SK280736B6 - Sulfonylaminopyridíny, spôsob ich výroby, použitie - Google Patents
Sulfonylaminopyridíny, spôsob ich výroby, použitie Download PDFInfo
- Publication number
- SK280736B6 SK280736B6 SK779-94A SK77994A SK280736B6 SK 280736 B6 SK280736 B6 SK 280736B6 SK 77994 A SK77994 A SK 77994A SK 280736 B6 SK280736 B6 SK 280736B6
- Authority
- SK
- Slovakia
- Prior art keywords
- yloxy
- pyrimidin
- methoxyphenoxy
- ethyl ester
- tert
- Prior art date
Links
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 44
- 238000000034 method Methods 0.000 title claims abstract description 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 105
- 150000001875 compounds Chemical class 0.000 claims abstract description 100
- 102000002045 Endothelin Human genes 0.000 claims abstract description 10
- 108050009340 Endothelin Proteins 0.000 claims abstract description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 10
- ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 claims abstract description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 10
- 150000003839 salts Chemical class 0.000 claims abstract description 10
- 230000000694 effects Effects 0.000 claims abstract description 9
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 claims abstract description 8
- 125000001424 substituent group Chemical group 0.000 claims abstract description 8
- 239000012948 isocyanate Substances 0.000 claims abstract description 6
- 150000002513 isocyanates Chemical class 0.000 claims abstract description 6
- 239000003814 drug Substances 0.000 claims abstract description 5
- 238000011282 treatment Methods 0.000 claims abstract description 4
- CKDWPUIZGOQOOM-UHFFFAOYSA-N Carbamyl chloride Chemical compound NC(Cl)=O CKDWPUIZGOQOOM-UHFFFAOYSA-N 0.000 claims abstract description 3
- 206010047163 Vasospasm Diseases 0.000 claims abstract description 3
- 208000028867 ischemia Diseases 0.000 claims abstract description 3
- 206010002383 Angina Pectoris Diseases 0.000 claims abstract 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract 2
- -1 carboxy, amino Chemical group 0.000 claims description 618
- 125000004494 ethyl ester group Chemical group 0.000 claims description 148
- 125000000217 alkyl group Chemical group 0.000 claims description 94
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 61
- OUCYWJAACMAXQD-UHFFFAOYSA-N pyridin-2-ylcarbamic acid Chemical compound OC(=O)NC1=CC=CC=N1 OUCYWJAACMAXQD-UHFFFAOYSA-N 0.000 claims description 59
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 56
- 125000003545 alkoxy group Chemical group 0.000 claims description 54
- 239000002253 acid Substances 0.000 claims description 42
- BHEVMLMGZDDWHX-UHFFFAOYSA-N 2-(sulfonylamino)pyridine Chemical class O=S(=O)=NC1=CC=CC=N1 BHEVMLMGZDDWHX-UHFFFAOYSA-N 0.000 claims description 26
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 25
- 229910052739 hydrogen Inorganic materials 0.000 claims description 24
- 239000001257 hydrogen Substances 0.000 claims description 22
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 15
- 229910052736 halogen Inorganic materials 0.000 claims description 14
- 150000002367 halogens Chemical class 0.000 claims description 14
- 150000002431 hydrogen Chemical class 0.000 claims description 14
- FKSXRCPGQMOMBI-UHFFFAOYSA-N pyridin-4-ylcarbamic acid Chemical compound OC(=O)NC1=CC=NC=C1 FKSXRCPGQMOMBI-UHFFFAOYSA-N 0.000 claims description 13
- 125000004414 alkyl thio group Chemical group 0.000 claims description 12
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
- 125000003118 aryl group Chemical group 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 8
- 125000000623 heterocyclic group Chemical group 0.000 claims description 8
- SZBFVXBLXXAOFZ-UHFFFAOYSA-N thiophen-3-ylcarbamic acid Chemical compound OC(=O)NC=1C=CSC=1 SZBFVXBLXXAOFZ-UHFFFAOYSA-N 0.000 claims description 8
- 125000006627 ethoxycarbonylamino group Chemical group 0.000 claims description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 6
- FTLCLAFMYWOANF-UHFFFAOYSA-N (2-fluorophenyl)carbamic acid Chemical compound OC(=O)NC1=CC=CC=C1F FTLCLAFMYWOANF-UHFFFAOYSA-N 0.000 claims description 5
- 125000003282 alkyl amino group Chemical group 0.000 claims description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- 150000002148 esters Chemical class 0.000 claims description 5
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 5
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 5
- LOGAFLFGWNBIIG-UHFFFAOYSA-N pyridin-3-ylcarbamic acid Chemical compound OC(=O)NC1=CC=CN=C1 LOGAFLFGWNBIIG-UHFFFAOYSA-N 0.000 claims description 5
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 5
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 4
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- PWXJULSLLONQHY-UHFFFAOYSA-N phenylcarbamic acid Chemical compound OC(=O)NC1=CC=CC=C1 PWXJULSLLONQHY-UHFFFAOYSA-N 0.000 claims description 4
- BWIXUZRDKXLWKB-UHFFFAOYSA-N pyrazin-2-ylcarbamic acid Chemical compound OC(=O)NC1=CN=CC=N1 BWIXUZRDKXLWKB-UHFFFAOYSA-N 0.000 claims description 4
- 125000005493 quinolyl group Chemical group 0.000 claims description 4
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 3
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
- 125000003342 alkenyl group Chemical group 0.000 claims description 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 3
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- CDNCYEYRGTVHJQ-UHFFFAOYSA-N furan-2-ylcarbamic acid Chemical compound OC(=O)NC1=CC=CO1 CDNCYEYRGTVHJQ-UHFFFAOYSA-N 0.000 claims description 3
- DDPSQFMPZPDBFP-UHFFFAOYSA-N furan-3-ylcarbamic acid Chemical compound OC(=O)NC=1C=COC=1 DDPSQFMPZPDBFP-UHFFFAOYSA-N 0.000 claims description 3
- 125000002883 imidazolyl group Chemical group 0.000 claims description 3
- 125000001041 indolyl group Chemical group 0.000 claims description 3
- 125000005956 isoquinolyl group Chemical group 0.000 claims description 3
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 3
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims description 3
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 3
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 3
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 3
- 125000000335 thiazolyl group Chemical group 0.000 claims description 3
- 125000001544 thienyl group Chemical group 0.000 claims description 3
- KNTZCGBYFGEMFR-UHFFFAOYSA-N (propan-2-ylazaniumyl)formate Chemical compound CC(C)NC(O)=O KNTZCGBYFGEMFR-UHFFFAOYSA-N 0.000 claims description 2
- 125000001137 3-hydroxypropoxy group Chemical group [H]OC([H])([H])C([H])([H])C([H])([H])O* 0.000 claims description 2
- 206010020852 Hypertonia Diseases 0.000 claims description 2
- 125000005036 alkoxyphenyl group Chemical group 0.000 claims description 2
- 125000005133 alkynyloxy group Chemical group 0.000 claims description 2
- 125000001769 aryl amino group Chemical group 0.000 claims description 2
- 125000005110 aryl thio group Chemical group 0.000 claims description 2
- 125000003725 azepanyl group Chemical group 0.000 claims description 2
- OQQXGCLLMDQESN-UHFFFAOYSA-N cyclohexylcarbamic acid Chemical compound OC(=O)NC1CCCCC1 OQQXGCLLMDQESN-UHFFFAOYSA-N 0.000 claims description 2
- RPJQHJLOMYJUHA-UHFFFAOYSA-N ethyl n-pyridin-4-ylcarbamate Chemical compound CCOC(=O)NC1=CC=NC=C1 RPJQHJLOMYJUHA-UHFFFAOYSA-N 0.000 claims description 2
- 125000002971 oxazolyl group Chemical group 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 2
- 125000005936 piperidyl group Chemical group 0.000 claims description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 claims 2
- QENMPTUFXWVPQZ-UHFFFAOYSA-N (2-hydroxyethylazaniumyl)formate Chemical compound OCCNC(O)=O QENMPTUFXWVPQZ-UHFFFAOYSA-N 0.000 claims 1
- TZFXPXHQMKMWGE-UHFFFAOYSA-N 1,3-benzodioxol-5-ylcarbamic acid Chemical compound OC(=O)NC1=CC=C2OCOC2=C1 TZFXPXHQMKMWGE-UHFFFAOYSA-N 0.000 claims 1
- WKYGWEBNPJJQLE-UHFFFAOYSA-N 2-[6-[(4-tert-butylphenyl)sulfonylamino]-5-(2-chloro-5-methoxyphenoxy)pyrimidin-4-yl]oxyethyl N-(1-methylpyridin-1-ium-4-yl)carbamate iodide Chemical compound [I-].C(C)(C)(C)C1=CC=C(C=C1)S(=O)(=O)NC1=C(C(=NC=N1)OCCOC(=O)NC1=CC=[N+](C=C1)C)OC1=C(C=CC(=C1)OC)Cl WKYGWEBNPJJQLE-UHFFFAOYSA-N 0.000 claims 1
- WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 claims 1
- GAWCRULEMQFHTI-UHFFFAOYSA-N 4-chlorophenylisocyanic acid Natural products OC(=O)NC1=CC=C(Cl)C=C1 GAWCRULEMQFHTI-UHFFFAOYSA-N 0.000 claims 1
- 239000005711 Benzoic acid Substances 0.000 claims 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims 1
- QOSMNYMQXIVWKY-UHFFFAOYSA-N Propyl levulinate Chemical compound CCCOC(=O)CCC(C)=O QOSMNYMQXIVWKY-UHFFFAOYSA-N 0.000 claims 1
- 239000013543 active substance Substances 0.000 claims 1
- 125000004104 aryloxy group Chemical group 0.000 claims 1
- 239000012050 conventional carrier Substances 0.000 claims 1
- QRKMGCXMJZJTGC-UHFFFAOYSA-N ethyl n-pyridin-2-ylcarbamate Chemical compound CCOC(=O)NC1=CC=CC=N1 QRKMGCXMJZJTGC-UHFFFAOYSA-N 0.000 claims 1
- YLRSARVOZNPQKX-UHFFFAOYSA-N ethyl n-pyridin-3-ylcarbamate Chemical compound CCOC(=O)NC1=CC=CN=C1 YLRSARVOZNPQKX-UHFFFAOYSA-N 0.000 claims 1
- YDLPENUJNOUHKW-UHFFFAOYSA-N ethyl pyridin-3-ylmethyl carbonate Chemical compound C(OCC1=CN=CC=C1)(OCC)=O YDLPENUJNOUHKW-UHFFFAOYSA-N 0.000 claims 1
- KWBIXTIBYFUAGV-UHFFFAOYSA-N ethylcarbamic acid Chemical compound CCNC(O)=O KWBIXTIBYFUAGV-UHFFFAOYSA-N 0.000 claims 1
- RRIWSQXXBIFKQM-UHFFFAOYSA-N monomeric N-benzylcarbamic acid Natural products OC(=O)NCC1=CC=CC=C1 RRIWSQXXBIFKQM-UHFFFAOYSA-N 0.000 claims 1
- STUHQDIOZQUPGP-UHFFFAOYSA-N morpholin-4-ium-4-carboxylate Chemical compound OC(=O)N1CCOCC1 STUHQDIOZQUPGP-UHFFFAOYSA-N 0.000 claims 1
- IHDRVAVNEDBQFF-UHFFFAOYSA-N quinolin-2-ylcarbamic acid Chemical compound C1=CC=CC2=NC(NC(=O)O)=CC=C21 IHDRVAVNEDBQFF-UHFFFAOYSA-N 0.000 claims 1
- WPWXYQIMXTUMJB-UHFFFAOYSA-N tert-butyl 3-(aminomethyl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC(CN)C1 WPWXYQIMXTUMJB-UHFFFAOYSA-N 0.000 claims 1
- 206010020772 Hypertension Diseases 0.000 abstract description 3
- 239000000969 carrier Substances 0.000 abstract description 3
- FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 abstract description 2
- 208000035475 disorder Diseases 0.000 abstract 2
- 239000000470 constituent Substances 0.000 abstract 1
- 239000007858 starting material Substances 0.000 description 61
- 239000000243 solution Substances 0.000 description 42
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 40
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
- RUEMLKUMKKDJTF-UHFFFAOYSA-N (2z)-n-diazoniopyridine-2-carboximidate Chemical compound [N-]=[N+]=NC(=O)C1=CC=CC=N1 RUEMLKUMKKDJTF-UHFFFAOYSA-N 0.000 description 32
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- 239000000460 chlorine Substances 0.000 description 22
- 229940124530 sulfonamide Drugs 0.000 description 20
- 239000002904 solvent Substances 0.000 description 19
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 18
- 235000019439 ethyl acetate Nutrition 0.000 description 18
- 239000000741 silica gel Substances 0.000 description 18
- 229910002027 silica gel Inorganic materials 0.000 description 18
- XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 17
- 239000012074 organic phase Substances 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- VYMROWZUHYKURR-UHFFFAOYSA-N pyridine-4-carbonyl azide Chemical compound [N-]=[N+]=NC(=O)C1=CC=NC=C1 VYMROWZUHYKURR-UHFFFAOYSA-N 0.000 description 14
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- 239000011541 reaction mixture Substances 0.000 description 11
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 11
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 10
- 238000007127 saponification reaction Methods 0.000 description 10
- JHTLPSNDZNHQDZ-UHFFFAOYSA-N 1,3-benzodioxole-5-sulfonamide Chemical compound NS(=O)(=O)C1=CC=C2OCOC2=C1 JHTLPSNDZNHQDZ-UHFFFAOYSA-N 0.000 description 9
- KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 9
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 9
- 239000003480 eluent Substances 0.000 description 9
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
- 239000013078 crystal Substances 0.000 description 8
- ZNSIOEUWGZNHAQ-UHFFFAOYSA-N (3e)-n-diazoniopyridine-3-carboximidate Chemical compound [N-]=[N+]=NC(=O)C1=CC=CN=C1 ZNSIOEUWGZNHAQ-UHFFFAOYSA-N 0.000 description 7
- ZNXOKLWCOWOECF-UHFFFAOYSA-N 4-tert-butyl-n-[6-(2-hydroxyethoxy)-5-(3-methoxyphenoxy)pyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC(OC=2C(=NC=NC=2NS(=O)(=O)C=2C=CC(=CC=2)C(C)(C)C)OCCO)=C1 ZNXOKLWCOWOECF-UHFFFAOYSA-N 0.000 description 7
- VIJHARLWDARHNW-UHFFFAOYSA-N N1=C(C=CC=C1)NC(O)=O.N1=C(C=CC=C1)C(=O)N=[N+]=[N-] Chemical compound N1=C(C=CC=C1)NC(O)=O.N1=C(C=CC=C1)C(=O)N=[N+]=[N-] VIJHARLWDARHNW-UHFFFAOYSA-N 0.000 description 7
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 7
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 7
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 7
- 150000003254 radicals Chemical class 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 6
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 6
- 238000002425 crystallisation Methods 0.000 description 6
- 230000008025 crystallization Effects 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- RYTRWDVNPIYXCQ-UHFFFAOYSA-N 4,6-dichloro-5-(2-chloro-5-methoxyphenoxy)pyrimidine Chemical compound COC1=CC=C(Cl)C(OC=2C(=NC=NC=2Cl)Cl)=C1 RYTRWDVNPIYXCQ-UHFFFAOYSA-N 0.000 description 5
- KYDZEZNYRFJCSA-UHFFFAOYSA-N 4-tert-butylbenzenesulfonamide Chemical compound CC(C)(C)C1=CC=C(S(N)(=O)=O)C=C1 KYDZEZNYRFJCSA-UHFFFAOYSA-N 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 5
- XPOLVIIHTDKJRY-UHFFFAOYSA-N acetic acid;methanimidamide Chemical compound NC=N.CC(O)=O XPOLVIIHTDKJRY-UHFFFAOYSA-N 0.000 description 5
- 150000001540 azides Chemical class 0.000 description 5
- RXQFSKAWABBDNG-UHFFFAOYSA-N disodium;ethane-1,2-diolate Chemical compound [Na+].[Na+].[O-]CC[O-] RXQFSKAWABBDNG-UHFFFAOYSA-N 0.000 description 5
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- CLKLYTYKDNXOJG-UHFFFAOYSA-N n-[5-(2-chloro-5-methoxyphenoxy)-6-(2-hydroxyethoxy)pyrimidin-4-yl]-1,3-benzodioxole-5-sulfonamide Chemical compound COC1=CC=C(Cl)C(OC=2C(=NC=NC=2NS(=O)(=O)C=2C=C3OCOC3=CC=2)OCCO)=C1 CLKLYTYKDNXOJG-UHFFFAOYSA-N 0.000 description 5
- DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 5
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 4
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 4
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- WFDIJRYMOXRFFG-UHFFFAOYSA-N acetic acid anhydride Natural products CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 238000000354 decomposition reaction Methods 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- XQBZLLGGLUHFNK-UHFFFAOYSA-N n-[5-(2-chloro-5-methoxyphenoxy)-6-(2-hydroxyethoxy)pyrimidin-4-yl]-4-methoxy-3-(2-morpholin-4-yl-2-oxoethoxy)benzenesulfonamide Chemical compound COC1=CC=C(Cl)C(OC=2C(=NC=NC=2NS(=O)(=O)C=2C=C(OCC(=O)N3CCOCC3)C(OC)=CC=2)OCCO)=C1 XQBZLLGGLUHFNK-UHFFFAOYSA-N 0.000 description 4
- SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 239000000376 reactant Substances 0.000 description 4
- 150000003456 sulfonamides Chemical class 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- IKHOFSYYOKPAKV-UHFFFAOYSA-N 2-[2-[6-[(4-tert-butylphenyl)sulfonylamino]-5-(3-methoxyphenoxy)pyrimidin-4-yl]oxyethoxycarbonylamino]acetic acid Chemical compound COC1=CC=CC(OC=2C(=NC=NC=2NS(=O)(=O)C=2C=CC(=CC=2)C(C)(C)C)OCCOC(=O)NCC(O)=O)=C1 IKHOFSYYOKPAKV-UHFFFAOYSA-N 0.000 description 3
- IZGOBGVYADHVKH-UHFFFAOYSA-N 4,6-dichloro-5-(2-methoxyphenoxy)-2-pyrimidin-2-ylpyrimidine Chemical compound COC1=CC=CC=C1OC1=C(Cl)N=C(C=2N=CC=CN=2)N=C1Cl IZGOBGVYADHVKH-UHFFFAOYSA-N 0.000 description 3
- FUYIWALKTPDJRC-UHFFFAOYSA-N 4-tert-butyl-n-[5-(2-chloro-5-methoxyphenoxy)-6-(2-hydroxyethoxy)-2-methylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=C(Cl)C(OC=2C(=NC(C)=NC=2NS(=O)(=O)C=2C=CC(=CC=2)C(C)(C)C)OCCO)=C1 FUYIWALKTPDJRC-UHFFFAOYSA-N 0.000 description 3
- UXIBNCWXEPUEFT-UHFFFAOYSA-N 4-tert-butyl-n-[5-(2-chloro-5-methoxyphenoxy)-6-(2-hydroxyethoxy)pyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=C(Cl)C(OC=2C(=NC=NC=2NS(=O)(=O)C=2C=CC(=CC=2)C(C)(C)C)OCCO)=C1 UXIBNCWXEPUEFT-UHFFFAOYSA-N 0.000 description 3
- QYNCNVIUQQJRPW-UHFFFAOYSA-N 4-tert-butyl-n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenyl)sulfanyl-2-pyrimidin-2-ylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1SC(C(=NC(=N1)C=2N=CC=CN=2)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 QYNCNVIUQQJRPW-UHFFFAOYSA-N 0.000 description 3
- KCBWAFJCKVKYHO-UHFFFAOYSA-N 6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-[[4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrazolo[3,4-d]pyrimidine Chemical compound C1(CC1)C1=NC=NC(=C1C1=NC=C2C(=N1)N(N=C2)CC1=CC=C(C=C1)C=1N(C=C(N=1)C(F)(F)F)C(C)C)OC KCBWAFJCKVKYHO-UHFFFAOYSA-N 0.000 description 3
- 244000215068 Acacia senegal Species 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 102000010180 Endothelin receptor Human genes 0.000 description 3
- 108050001739 Endothelin receptor Proteins 0.000 description 3
- 229920000084 Gum arabic Polymers 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000007983 Tris buffer Substances 0.000 description 3
- 239000000205 acacia gum Substances 0.000 description 3
- 235000010489 acacia gum Nutrition 0.000 description 3
- 230000029936 alkylation Effects 0.000 description 3
- 238000005804 alkylation reaction Methods 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 239000005557 antagonist Substances 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 230000004872 arterial blood pressure Effects 0.000 description 3
- 230000036772 blood pressure Effects 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 239000006260 foam Substances 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- TWBYWOBDOCUKOW-UHFFFAOYSA-N isonicotinic acid Chemical compound OC(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-N 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 3
- DJJFEUMLVJZCSB-UHFFFAOYSA-N n-[5-(3,5-dimethoxyphenoxy)-6-(2-hydroxyethoxy)pyrimidin-4-yl]-1,3-benzodioxole-5-sulfonamide Chemical compound COC1=CC(OC)=CC(OC=2C(=NC=NC=2NS(=O)(=O)C=2C=C3OCOC3=CC=2)OCCO)=C1 DJJFEUMLVJZCSB-UHFFFAOYSA-N 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 229940023144 sodium glycolate Drugs 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 3
- JEJAMASKDTUEBZ-UHFFFAOYSA-N tris(1,1,3-tribromo-2,2-dimethylpropyl) phosphate Chemical compound BrCC(C)(C)C(Br)(Br)OP(=O)(OC(Br)(Br)C(C)(C)CBr)OC(Br)(Br)C(C)(C)CBr JEJAMASKDTUEBZ-UHFFFAOYSA-N 0.000 description 3
- VZNCSZQPNIEEMN-UHFFFAOYSA-N 1-fluoro-2-isocyanatobenzene Chemical compound FC1=CC=CC=C1N=C=O VZNCSZQPNIEEMN-UHFFFAOYSA-N 0.000 description 2
- OAMPULWQGDEOHG-UHFFFAOYSA-N 2,3-dihydro-1,4-benzodioxine-6-sulfonamide Chemical compound O1CCOC2=CC(S(=O)(=O)N)=CC=C21 OAMPULWQGDEOHG-UHFFFAOYSA-N 0.000 description 2
- QTHKBPBUZDZVRZ-UHFFFAOYSA-N 2-(4-chlorosulfonylphenoxy)ethyl acetate Chemical compound CC(=O)OCCOC1=CC=C(S(Cl)(=O)=O)C=C1 QTHKBPBUZDZVRZ-UHFFFAOYSA-N 0.000 description 2
- ISKFOTCTIJLSDJ-UHFFFAOYSA-N 2-[(2-chloro-5-methoxyphenoxy)methyl]-2-methylpropanedioic acid Chemical compound CC(COC1=C(C=CC(=C1)OC)Cl)(C(=O)O)C(=O)O ISKFOTCTIJLSDJ-UHFFFAOYSA-N 0.000 description 2
- SFPQDYSOPQHZAQ-UHFFFAOYSA-N 2-methoxypropanenitrile Chemical compound COC(C)C#N SFPQDYSOPQHZAQ-UHFFFAOYSA-N 0.000 description 2
- LULAYUGMBFYYEX-UHFFFAOYSA-N 3-chlorobenzoic acid Chemical compound OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 2
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
- AXEFPRJOGBGEKM-UHFFFAOYSA-N 3-methyl-1,2-oxazole-5-carbonyl azide Chemical compound CC=1C=C(C(=O)N=[N+]=[N-])ON=1 AXEFPRJOGBGEKM-UHFFFAOYSA-N 0.000 description 2
- MVQVNTPHUGQQHK-UHFFFAOYSA-N 3-pyridinemethanol Chemical compound OCC1=CC=CN=C1 MVQVNTPHUGQQHK-UHFFFAOYSA-N 0.000 description 2
- TWYRHWWVMQAIAE-UHFFFAOYSA-N 4,6-dichloro-5-(3-methoxyphenoxy)pyrimidine Chemical compound COC1=CC=CC(OC=2C(=NC=NC=2Cl)Cl)=C1 TWYRHWWVMQAIAE-UHFFFAOYSA-N 0.000 description 2
- CFKMVGJGLGKFKI-UHFFFAOYSA-N 4-chloro-m-cresol Chemical compound CC1=CC(O)=CC=C1Cl CFKMVGJGLGKFKI-UHFFFAOYSA-N 0.000 description 2
- IFRLGLFTKQDBHF-UHFFFAOYSA-N 4-cyclopropylbenzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1CC1 IFRLGLFTKQDBHF-UHFFFAOYSA-N 0.000 description 2
- YDUAOJPPBAUYDZ-UHFFFAOYSA-N 4-hydroxy-5-(2-methoxyphenyl)sulfanyl-1h-pyrimidin-6-one Chemical compound COC1=CC=CC=C1SC1=C(O)N=CNC1=O YDUAOJPPBAUYDZ-UHFFFAOYSA-N 0.000 description 2
- NQGKMCJOTRTORV-UHFFFAOYSA-N 4-tert-butyl-n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenyl)sulfanyl-2-methylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1SC(C(=NC(C)=N1)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 NQGKMCJOTRTORV-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- UUNDXNPWSXMSGP-UHFFFAOYSA-N COC1=CC=C(Cl)C(OC=2C(=NC=NC=2)NOCCO[Si](C)(C)C(C)(C)C)=C1 Chemical compound COC1=CC=C(Cl)C(OC=2C(=NC=NC=2)NOCCO[Si](C)(C)C(C)(C)C)=C1 UUNDXNPWSXMSGP-UHFFFAOYSA-N 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- 102100033902 Endothelin-1 Human genes 0.000 description 2
- 101800004490 Endothelin-1 Proteins 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- IDRGFNPZDVBSSE-UHFFFAOYSA-N OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F Chemical compound OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F IDRGFNPZDVBSSE-UHFFFAOYSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- SDMQYTZUNWOWIN-UHFFFAOYSA-N S1C=C(C=C1)NC(O)=O.S1C=C(C=C1)C(=O)N=[N+]=[N-] Chemical compound S1C=C(C=C1)NC(O)=O.S1C=C(C=C1)C(=O)N=[N+]=[N-] SDMQYTZUNWOWIN-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 239000000908 ammonium hydroxide Substances 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 239000012131 assay buffer Substances 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 206010008118 cerebral infarction Diseases 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 2
- CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- HYCDGBJBLNNWGB-UHFFFAOYSA-N n-[6-(2-aminoethoxy)-5-(2-chloro-5-methoxyphenoxy)pyrimidin-4-yl]-4-tert-butylbenzenesulfonamide Chemical compound COC1=CC=C(Cl)C(OC=2C(=NC=NC=2NS(=O)(=O)C=2C=CC(=CC=2)C(C)(C)C)OCCN)=C1 HYCDGBJBLNNWGB-UHFFFAOYSA-N 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- RLNGGCZBYFRNSV-UHFFFAOYSA-N pyrazine-2-carbonyl azide Chemical compound [N-]=[N+]=NC(=O)C1=CN=CC=N1 RLNGGCZBYFRNSV-UHFFFAOYSA-N 0.000 description 2
- SHNUBALDGXWUJI-UHFFFAOYSA-N pyridin-2-ylmethanol Chemical compound OCC1=CC=CC=N1 SHNUBALDGXWUJI-UHFFFAOYSA-N 0.000 description 2
- VSCGRMUDBNQJNB-UHFFFAOYSA-N pyrimidin-2-ylcarbamic acid Chemical compound OC(=O)NC1=NC=CC=N1 VSCGRMUDBNQJNB-UHFFFAOYSA-N 0.000 description 2
- 238000002390 rotary evaporation Methods 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 230000035939 shock Effects 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- YNVOMSDITJMNET-UHFFFAOYSA-N thiophene-3-carboxylic acid Chemical compound OC(=O)C=1C=CSC=1 YNVOMSDITJMNET-UHFFFAOYSA-N 0.000 description 2
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
- VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
- WBZKTGIFUVZJNX-UHFFFAOYSA-N (2-anilino-2-oxoethyl)carbamic acid Chemical compound OC(=O)NCC(=O)NC1=CC=CC=C1 WBZKTGIFUVZJNX-UHFFFAOYSA-N 0.000 description 1
- VDUQMRKYKLQPAT-UHFFFAOYSA-N (2-carbonazidoylphenyl) acetate Chemical compound CC(=O)OC1=CC=CC=C1C(=O)N=[N+]=[N-] VDUQMRKYKLQPAT-UHFFFAOYSA-N 0.000 description 1
- NMELKTWAMSTJPD-UHFFFAOYSA-N (2-hydroxyphenyl)carbamic acid Chemical compound OC(=O)NC1=CC=CC=C1O NMELKTWAMSTJPD-UHFFFAOYSA-N 0.000 description 1
- ZUJGUMQUYCWBGQ-UHFFFAOYSA-N (2-morpholin-4-yl-2-oxoethyl)carbamic acid Chemical compound OC(=O)NCC(=O)N1CCOCC1 ZUJGUMQUYCWBGQ-UHFFFAOYSA-N 0.000 description 1
- JKSVQADQPPQJCR-UHFFFAOYSA-N (3-methyl-1,2-oxazol-5-yl)carbamic acid Chemical compound CC=1C=C(NC(O)=O)ON=1 JKSVQADQPPQJCR-UHFFFAOYSA-N 0.000 description 1
- MAYZWDRUFKUGGP-VIFPVBQESA-N (3s)-1-[5-tert-butyl-3-[(1-methyltetrazol-5-yl)methyl]triazolo[4,5-d]pyrimidin-7-yl]pyrrolidin-3-ol Chemical compound CN1N=NN=C1CN1C2=NC(C(C)(C)C)=NC(N3C[C@@H](O)CC3)=C2N=N1 MAYZWDRUFKUGGP-VIFPVBQESA-N 0.000 description 1
- MOWXJLUYGFNTAL-DEOSSOPVSA-N (s)-[2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxypyridazin-3-yl)methanol Chemical compound N1=NC(OC)=CC=C1[C@@H](O)C1=CC(C=2C3=CC=C(C=C3N=CN=2)N2CCOCC2)=C(F)C=C1Cl MOWXJLUYGFNTAL-DEOSSOPVSA-N 0.000 description 1
- DEVSOMFAQLZNKR-RJRFIUFISA-N (z)-3-[3-[3,5-bis(trifluoromethyl)phenyl]-1,2,4-triazol-1-yl]-n'-pyrazin-2-ylprop-2-enehydrazide Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(C2=NN(\C=C/C(=O)NNC=3N=CC=NC=3)C=N2)=C1 DEVSOMFAQLZNKR-RJRFIUFISA-N 0.000 description 1
- FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 description 1
- FSISZPWQLFHTPZ-UHFFFAOYSA-N 1,3-benzodioxole-5-carbonyl azide Chemical compound [N-]=[N+]=NC(=O)C1=CC=C2OCOC2=C1 FSISZPWQLFHTPZ-UHFFFAOYSA-N 0.000 description 1
- QPFOQFYKGLINPR-UHFFFAOYSA-N 1,3-thiazol-2-ylcarbamic acid Chemical compound OC(=O)NC1=NC=CS1 QPFOQFYKGLINPR-UHFFFAOYSA-N 0.000 description 1
- CGOULUCSFQWTDF-UHFFFAOYSA-N 1-(2-methoxyphenyl)-3-morpholin-4-ylpropan-2-one Chemical compound COC1=CC=CC=C1CC(=O)CN1CCOCC1 CGOULUCSFQWTDF-UHFFFAOYSA-N 0.000 description 1
- USPJMQKQRDANDG-UHFFFAOYSA-N 1-(2-methoxyphenyl)-3-piperidin-1-ylpropan-2-one Chemical compound COC1=CC=CC=C1CC(=O)CN1CCCCC1 USPJMQKQRDANDG-UHFFFAOYSA-N 0.000 description 1
- IRBOPMAYONEFAV-UHFFFAOYSA-N 1-(3-methoxyphenyl)-3-morpholin-4-ylpropan-2-one Chemical compound COC1=CC=CC(CC(=O)CN2CCOCC2)=C1 IRBOPMAYONEFAV-UHFFFAOYSA-N 0.000 description 1
- ABDDQTDRAHXHOC-QMMMGPOBSA-N 1-[(7s)-5,7-dihydro-4h-thieno[2,3-c]pyran-7-yl]-n-methylmethanamine Chemical compound CNC[C@@H]1OCCC2=C1SC=C2 ABDDQTDRAHXHOC-QMMMGPOBSA-N 0.000 description 1
- ADAKRBAJFHTIEW-UHFFFAOYSA-N 1-chloro-4-isocyanatobenzene Chemical compound ClC1=CC=C(N=C=O)C=C1 ADAKRBAJFHTIEW-UHFFFAOYSA-N 0.000 description 1
- SDGMUBWPXBSKCT-UHFFFAOYSA-N 1-chloro-4-methoxy-2-methylbenzene Chemical compound COC1=CC=C(Cl)C(C)=C1 SDGMUBWPXBSKCT-UHFFFAOYSA-N 0.000 description 1
- RIKWVZGZRYDACA-UHFFFAOYSA-N 1-fluoro-3-isocyanatobenzene Chemical compound FC1=CC=CC(N=C=O)=C1 RIKWVZGZRYDACA-UHFFFAOYSA-N 0.000 description 1
- SUVCZZADQDCIEQ-UHFFFAOYSA-N 1-isocyanato-2-methoxybenzene Chemical compound COC1=CC=CC=C1N=C=O SUVCZZADQDCIEQ-UHFFFAOYSA-N 0.000 description 1
- NPOVTGVGOBJZPY-UHFFFAOYSA-N 1-isocyanato-3-methoxybenzene Chemical compound COC1=CC=CC(N=C=O)=C1 NPOVTGVGOBJZPY-UHFFFAOYSA-N 0.000 description 1
- CPPGZWWUPFWALU-UHFFFAOYSA-N 1-isocyanato-3-methylbenzene Chemical compound CC1=CC=CC(N=C=O)=C1 CPPGZWWUPFWALU-UHFFFAOYSA-N 0.000 description 1
- QZTWVDCKDWZCLV-UHFFFAOYSA-N 1-isocyanato-4-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=C(N=C=O)C=C1 QZTWVDCKDWZCLV-UHFFFAOYSA-N 0.000 description 1
- CZJTWOHPFAGVSN-UHFFFAOYSA-N 1-methylpyrrole-2-carbonyl azide Chemical compound CN1C=CC=C1C(=O)N=[N+]=[N-] CZJTWOHPFAGVSN-UHFFFAOYSA-N 0.000 description 1
- ILAOVOOZLVGAJF-UHFFFAOYSA-N 1-methylpyrrole-2-carboxylic acid Chemical compound CN1C=CC=C1C(O)=O ILAOVOOZLVGAJF-UHFFFAOYSA-N 0.000 description 1
- LBEZQIFOXHJHDY-UHFFFAOYSA-N 1-morpholin-4-yl-2-phenoxyethanone Chemical compound C1COCCN1C(=O)COC1=CC=CC=C1 LBEZQIFOXHJHDY-UHFFFAOYSA-N 0.000 description 1
- UYUYDGNUIQSIJW-UHFFFAOYSA-N 1-morpholin-4-yl-3-phenylpropan-1-one Chemical compound C1COCCN1C(=O)CCC1=CC=CC=C1 UYUYDGNUIQSIJW-UHFFFAOYSA-N 0.000 description 1
- LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 description 1
- VVYQNDNLWMEVHV-UHFFFAOYSA-N 2-(2-methoxyphenoxy)-1-piperidin-1-ylethanone Chemical compound COC1=CC=CC=C1OCC(=O)N1CCCCC1 VVYQNDNLWMEVHV-UHFFFAOYSA-N 0.000 description 1
- IHONYPFTXGQWAX-UHFFFAOYSA-N 2-(2-methoxyphenoxy)acetic acid Chemical compound COC1=CC=CC=C1OCC(O)=O IHONYPFTXGQWAX-UHFFFAOYSA-N 0.000 description 1
- HEYJWMRBDCHCHX-UHFFFAOYSA-N 2-(2-methoxyphenyl)-1-morpholin-4-ylethanone Chemical compound COC1=CC=CC=C1CC(=O)N1CCOCC1 HEYJWMRBDCHCHX-UHFFFAOYSA-N 0.000 description 1
- BNOYRPYJHHKYKN-UHFFFAOYSA-N 2-(2-methoxyphenyl)sulfanylpropanedioic acid Chemical compound COC1=CC=CC=C1SC(C(O)=O)C(O)=O BNOYRPYJHHKYKN-UHFFFAOYSA-N 0.000 description 1
- GHKLXXBWQJOXKB-UHFFFAOYSA-N 2-(bromomethyl)-1-chloro-4-methoxybenzene Chemical compound COC1=CC=C(Cl)C(CBr)=C1 GHKLXXBWQJOXKB-UHFFFAOYSA-N 0.000 description 1
- HIEOUKHLYRIXGD-UHFFFAOYSA-N 2-[(2-methoxyphenoxy)methyl]-2-methylpropanedioic acid Chemical compound COC1=CC=CC=C1OCC(C)(C(O)=O)C(O)=O HIEOUKHLYRIXGD-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- XPOWMKNHKCJZNA-UHFFFAOYSA-N 2-[2-tert-butyl-6-[(4-tert-butylphenyl)sulfonylamino]-5-(2-methoxyphenoxy)pyrimidin-4-yl]oxyethyl n-pyridin-2-ylcarbamate Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C(C)(C)C)OCCOC(=O)NC=2N=CC=CC=2)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 XPOWMKNHKCJZNA-UHFFFAOYSA-N 0.000 description 1
- PFOQIHIIOLBCEQ-UHFFFAOYSA-N 2-[4-[2-(2,6-dimethoxyphenyl)-7-methyl-3h-benzimidazol-5-yl]piperidin-1-yl]-n-methylethanamine Chemical compound C1CN(CCNC)CCC1C1=CC(C)=C(NC(=N2)C=3C(=CC=CC=3OC)OC)C2=C1 PFOQIHIIOLBCEQ-UHFFFAOYSA-N 0.000 description 1
- FESZVWYEEWPCRF-UHFFFAOYSA-N 2-[5-(2-methoxyphenoxy)-6-[[4-(2-methylpropyl)phenyl]sulfonylamino]-2-pyrimidin-2-ylpyrimidin-4-yl]oxyethyl morpholine-4-carboxylate Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2N=CC=CN=2)OCCOC(=O)N2CCOCC2)=C1NS(=O)(=O)C1=CC=C(CC(C)C)C=C1 FESZVWYEEWPCRF-UHFFFAOYSA-N 0.000 description 1
- NNLKMQXTQXTMET-UHFFFAOYSA-N 2-[6-[(4-tert-butylphenyl)sulfonylamino]-5-(2-methoxyphenoxy)-2-methylpyrimidin-4-yl]oxyethyl n-pyridin-2-ylcarbamate Chemical compound COC1=CC=CC=C1OC(C(=NC(C)=N1)OCCOC(=O)NC=2N=CC=CC=2)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 NNLKMQXTQXTMET-UHFFFAOYSA-N 0.000 description 1
- MHTJUPCJZWJYIS-UHFFFAOYSA-N 2-[6-[(4-tert-butylphenyl)sulfonylamino]-5-(3-methoxyphenoxy)pyrimidin-4-yl]oxyethyl morpholine-4-carboxylate Chemical compound COC1=CC=CC(OC=2C(=NC=NC=2NS(=O)(=O)C=2C=CC(=CC=2)C(C)(C)C)OCCOC(=O)N2CCOCC2)=C1 MHTJUPCJZWJYIS-UHFFFAOYSA-N 0.000 description 1
- UVQWRTRNHHLFOD-UHFFFAOYSA-N 2-[6-[[4-(2-hydroxyethoxy)phenyl]sulfonylamino]-5-(2-methoxyphenoxy)pyrimidin-4-yl]oxyethyl n-phenylcarbamate Chemical compound COC1=CC=CC=C1OC(C(=NC=N1)OCCOC(=O)NC=2C=CC=CC=2)=C1NS(=O)(=O)C1=CC=C(OCCO)C=C1 UVQWRTRNHHLFOD-UHFFFAOYSA-N 0.000 description 1
- BHKJPUSGXPRDPB-UHFFFAOYSA-N 2-[6-[[4-(2-hydroxyethoxy)phenyl]sulfonylamino]-5-(2-methoxyphenoxy)pyrimidin-4-yl]oxyethyl n-pyridin-3-ylcarbamate Chemical compound COC1=CC=CC=C1OC(C(=NC=N1)OCCOC(=O)NC=2C=NC=CC=2)=C1NS(=O)(=O)C1=CC=C(OCCO)C=C1 BHKJPUSGXPRDPB-UHFFFAOYSA-N 0.000 description 1
- DIABUJYZLNKYQJ-UHFFFAOYSA-N 2-azidopyridine Chemical compound [N-]=[N+]=NC1=CC=CC=N1 DIABUJYZLNKYQJ-UHFFFAOYSA-N 0.000 description 1
- 125000006016 2-bromoethoxy group Chemical group 0.000 description 1
- MEAYPBQBXNTXBT-UHFFFAOYSA-N 2-chloro-5-methoxybenzenesulfonyl chloride Chemical compound COC1=CC=C(Cl)C(S(Cl)(=O)=O)=C1 MEAYPBQBXNTXBT-UHFFFAOYSA-N 0.000 description 1
- KULSVCANYQIOFD-UHFFFAOYSA-N 2-chloro-5-methoxyphenol Chemical compound COC1=CC=C(Cl)C(O)=C1 KULSVCANYQIOFD-UHFFFAOYSA-N 0.000 description 1
- GSLTVFIVJMCNBH-UHFFFAOYSA-N 2-isocyanatopropane Chemical compound CC(C)N=C=O GSLTVFIVJMCNBH-UHFFFAOYSA-N 0.000 description 1
- QKPVEISEHYYHRH-UHFFFAOYSA-N 2-methoxyacetonitrile Chemical compound COCC#N QKPVEISEHYYHRH-UHFFFAOYSA-N 0.000 description 1
- HLGNKWVNJVYHJO-UHFFFAOYSA-N 2-methoxybutanenitrile Chemical compound CCC(OC)C#N HLGNKWVNJVYHJO-UHFFFAOYSA-N 0.000 description 1
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 1
- WHFKYDMBUMLWDA-UHFFFAOYSA-N 2-phenoxyethyl acetate Chemical compound CC(=O)OCCOC1=CC=CC=C1 WHFKYDMBUMLWDA-UHFFFAOYSA-N 0.000 description 1
- WDTCUCYYRCAAIW-UHFFFAOYSA-N 2-quinolin-2-ylacetyl azide Chemical compound C1=CC=CC2=NC(CC(=O)N=[N+]=[N-])=CC=C21 WDTCUCYYRCAAIW-UHFFFAOYSA-N 0.000 description 1
- MEZNPUULYGXXFL-UHFFFAOYSA-N 3,4-dimethoxybenzenesulfonamide Chemical compound COC1=CC=C(S(N)(=O)=O)C=C1OC MEZNPUULYGXXFL-UHFFFAOYSA-N 0.000 description 1
- HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 description 1
- JCIQDMUYVJOKGX-UHFFFAOYSA-N 3-(2-methoxyphenoxy)pyridine Chemical compound COC1=CC=CC=C1OC1=CC=CN=C1 JCIQDMUYVJOKGX-UHFFFAOYSA-N 0.000 description 1
- BYHQTRFJOGIQAO-GOSISDBHSA-N 3-(4-bromophenyl)-8-[(2R)-2-hydroxypropyl]-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C[C@H](CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)Br)O BYHQTRFJOGIQAO-GOSISDBHSA-N 0.000 description 1
- DRSVLMLVJLOPSP-UHFFFAOYSA-N 3-(4-chlorosulfonylphenoxy)propyl acetate Chemical compound CC(=O)OCCCOC1=CC=C(S(Cl)(=O)=O)C=C1 DRSVLMLVJLOPSP-UHFFFAOYSA-N 0.000 description 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
- SKBJYRPOZXOUIG-UHFFFAOYSA-N 3-(hydroxymethyl)pyridine-2-carboxylic acid Chemical compound OCC1=CC=CN=C1C(O)=O SKBJYRPOZXOUIG-UHFFFAOYSA-N 0.000 description 1
- WNEODWDFDXWOLU-QHCPKHFHSA-N 3-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2s)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]pyridin-2-yl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one Chemical compound C([C@@H](N(CC1)C=2C=NC(NC=3C(N(C)C=C(C=3)C=3C(=C(N4C(C5=CC=6CC(C)(C)CC=6N5CC4)=O)N=CC=3)CO)=O)=CC=2)C)N1C1COC1 WNEODWDFDXWOLU-QHCPKHFHSA-N 0.000 description 1
- ZICHEAWRQJUWKA-UHFFFAOYSA-N 3-isocyanatofuran Chemical compound O=C=NC=1C=COC=1 ZICHEAWRQJUWKA-UHFFFAOYSA-N 0.000 description 1
- SHVVSKCXWMEDRW-UHFFFAOYSA-N 3-isocyanatopyridine Chemical compound O=C=NC1=CC=CN=C1 SHVVSKCXWMEDRW-UHFFFAOYSA-N 0.000 description 1
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 1
- FZOXUFODEISZLN-UHFFFAOYSA-N 3-phenoxypropyl acetate Chemical compound CC(=O)OCCCOC1=CC=CC=C1 FZOXUFODEISZLN-UHFFFAOYSA-N 0.000 description 1
- UPYGQHFLOHFHPB-UHFFFAOYSA-N 4,6-dichloro-5-(2-chloro-5-methoxyphenoxy)-2-(2-methoxyethyl)pyrimidine Chemical compound ClC1=NC(CCOC)=NC(Cl)=C1OC1=CC(OC)=CC=C1Cl UPYGQHFLOHFHPB-UHFFFAOYSA-N 0.000 description 1
- XNESKGCRYAJBBO-UHFFFAOYSA-N 4,6-dichloro-5-(2-chloro-5-methoxyphenoxy)-2-(methoxymethyl)pyrimidine Chemical compound ClC1=NC(COC)=NC(Cl)=C1OC1=CC(OC)=CC=C1Cl XNESKGCRYAJBBO-UHFFFAOYSA-N 0.000 description 1
- BPXMOQLQXOLWKQ-UHFFFAOYSA-N 4,6-dichloro-5-(2-methoxyphenoxy)-2-phenylpyrimidine Chemical compound COC1=CC=CC=C1OC1=C(Cl)N=C(C=2C=CC=CC=2)N=C1Cl BPXMOQLQXOLWKQ-UHFFFAOYSA-N 0.000 description 1
- SDEPSILVDLKJOR-UHFFFAOYSA-N 4,6-dichloro-5-(2-methoxyphenyl)sulfanylpyrimidine Chemical compound COC1=CC=CC=C1SC1=C(Cl)N=CN=C1Cl SDEPSILVDLKJOR-UHFFFAOYSA-N 0.000 description 1
- WLMPRXAVBOOURE-UHFFFAOYSA-N 4,6-dichloro-5-(3,4-dimethoxyphenoxy)pyrimidine Chemical compound C1=C(OC)C(OC)=CC=C1OC1=C(Cl)N=CN=C1Cl WLMPRXAVBOOURE-UHFFFAOYSA-N 0.000 description 1
- JFZAHQRWOQIZIS-UHFFFAOYSA-N 4,6-dichloro-5-(3,5-dimethoxyphenoxy)pyrimidine Chemical compound COC1=CC(OC)=CC(OC=2C(=NC=NC=2Cl)Cl)=C1 JFZAHQRWOQIZIS-UHFFFAOYSA-N 0.000 description 1
- DUFGYCAXVIUXIP-UHFFFAOYSA-N 4,6-dihydroxypyrimidine Chemical compound OC1=CC(O)=NC=N1 DUFGYCAXVIUXIP-UHFFFAOYSA-N 0.000 description 1
- WAEDOYKLSKTBMS-UHFFFAOYSA-N 4-(2-bromoethoxy)benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=C(OCCBr)C=C1 WAEDOYKLSKTBMS-UHFFFAOYSA-N 0.000 description 1
- ONAFMGKEGKIIRF-UHFFFAOYSA-N 4-(3-morpholin-4-yl-3-oxopropyl)benzenesulfonyl chloride Chemical compound C1=CC(S(=O)(=O)Cl)=CC=C1CCC(=O)N1CCOCC1 ONAFMGKEGKIIRF-UHFFFAOYSA-N 0.000 description 1
- VNUVBVTWBBODSV-UHFFFAOYSA-N 4-(dimethylamino)benzenesulfonamide Chemical compound CN(C)C1=CC=C(S(N)(=O)=O)C=C1 VNUVBVTWBBODSV-UHFFFAOYSA-N 0.000 description 1
- TZVCRURTWPSQQH-UHFFFAOYSA-N 4-[2-(2-methoxyphenoxy)ethyl]morpholine Chemical compound COC1=CC=CC=C1OCCN1CCOCC1 TZVCRURTWPSQQH-UHFFFAOYSA-N 0.000 description 1
- CWHCZQKBHKEGDY-UHFFFAOYSA-N 4-[4,6-dichloro-5-(2-methoxyphenoxy)pyrimidin-2-yl]morpholine Chemical compound COC1=CC=CC=C1OC1=C(Cl)N=C(N2CCOCC2)N=C1Cl CWHCZQKBHKEGDY-UHFFFAOYSA-N 0.000 description 1
- CPOFXGQARDYCGK-UHFFFAOYSA-N 4-[4,6-dichloro-5-[(2-chloro-5-methoxyphenyl)methyl]pyrimidin-2-yl]morpholine Chemical compound COC1=CC=C(Cl)C(CC=2C(=NC(=NC=2Cl)N2CCOCC2)Cl)=C1 CPOFXGQARDYCGK-UHFFFAOYSA-N 0.000 description 1
- KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 description 1
- OLJWBDMXDZHRCL-UHFFFAOYSA-N 4-cyclopropyl-n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-pyrimidin-2-ylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2N=CC=CN=2)OCCO)=C1NS(=O)(=O)C1=CC=C(C2CC2)C=C1 OLJWBDMXDZHRCL-UHFFFAOYSA-N 0.000 description 1
- UBXDNWVNEZBDBN-UHFFFAOYSA-N 4-cyclopropylaniline Chemical compound C1=CC(N)=CC=C1C1CC1 UBXDNWVNEZBDBN-UHFFFAOYSA-N 0.000 description 1
- QCHUBTJEGZWBFJ-UHFFFAOYSA-N 4-cyclopropylbenzenesulfonyl chloride Chemical compound C1=CC(S(=O)(=O)Cl)=CC=C1C1CC1 QCHUBTJEGZWBFJ-UHFFFAOYSA-N 0.000 description 1
- GKGOIYMLPJJVQI-UHFFFAOYSA-N 4-ethenylbenzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=C(C=C)C=C1 GKGOIYMLPJJVQI-UHFFFAOYSA-N 0.000 description 1
- YBUHFDDJPWKFLD-UHFFFAOYSA-N 4-hydroxy-5-(2-methoxyphenyl)sulfanyl-2-pyrimidin-2-yl-1h-pyrimidin-6-one Chemical compound COC1=CC=CC=C1SC1=C(O)N=C(C=2N=CC=CN=2)NC1=O YBUHFDDJPWKFLD-UHFFFAOYSA-N 0.000 description 1
- GRIKNSHGKWLWSA-UHFFFAOYSA-N 4-methoxy-2-(3-morpholin-4-yl-3-oxopropyl)benzenesulfonamide Chemical compound COC1=CC=C(S(N)(=O)=O)C(CCC(=O)N2CCOCC2)=C1 GRIKNSHGKWLWSA-UHFFFAOYSA-N 0.000 description 1
- WHPYRCRUGUOPLZ-UHFFFAOYSA-N 4-methoxy-3-(2-morpholin-4-yl-2-oxoethoxy)benzenesulfonyl chloride Chemical compound COC1=CC=C(S(Cl)(=O)=O)C=C1OCC(=O)N1CCOCC1 WHPYRCRUGUOPLZ-UHFFFAOYSA-N 0.000 description 1
- KUXFFYBIYBENDH-UHFFFAOYSA-N 4-methoxy-3-(2-morpholin-4-yl-2-oxoethyl)benzenesulfonyl chloride Chemical compound COC1=CC=C(S(Cl)(=O)=O)C=C1CC(=O)N1CCOCC1 KUXFFYBIYBENDH-UHFFFAOYSA-N 0.000 description 1
- OOHULKULKQYKKU-UHFFFAOYSA-N 4-methoxy-3-(2-oxo-2-piperidin-1-ylethoxy)benzenesulfonyl chloride Chemical compound COC1=CC=C(S(Cl)(=O)=O)C=C1OCC(=O)N1CCCCC1 OOHULKULKQYKKU-UHFFFAOYSA-N 0.000 description 1
- WPNXVUMBOCPDGI-UHFFFAOYSA-N 4-methoxy-3-(3-morpholin-4-yl-3-oxopropyl)benzenesulfonyl chloride Chemical compound COC1=CC=C(S(Cl)(=O)=O)C=C1CCC(=O)N1CCOCC1 WPNXVUMBOCPDGI-UHFFFAOYSA-N 0.000 description 1
- PCADELVQHOSASI-UHFFFAOYSA-N 4-methoxy-3-(3-oxo-3-piperidin-1-ylpropyl)benzenesulfonyl chloride Chemical compound COC1=CC=C(S(Cl)(=O)=O)C=C1CCC(=O)N1CCCCC1 PCADELVQHOSASI-UHFFFAOYSA-N 0.000 description 1
- ITLKXKYLQIPXAP-UHFFFAOYSA-N 4-methoxy-3-propan-2-ylbenzenesulfonamide Chemical compound COC1=CC=C(S(N)(=O)=O)C=C1C(C)C ITLKXKYLQIPXAP-UHFFFAOYSA-N 0.000 description 1
- XDJAAZYHCCRJOK-UHFFFAOYSA-N 4-methoxybenzonitrile Chemical compound COC1=CC=C(C#N)C=C1 XDJAAZYHCCRJOK-UHFFFAOYSA-N 0.000 description 1
- DUIMWXDLDBNUFD-UHFFFAOYSA-N 4-pyrimidin-2-ylmorpholine Chemical compound C1COCCN1C1=NC=CC=N1 DUIMWXDLDBNUFD-UHFFFAOYSA-N 0.000 description 1
- YPNXXEIRGABVJB-UHFFFAOYSA-N 4-tert-butyl-n-[2-(2-chloro-5-methoxyphenoxy)-6-(2-hydroxyethoxy)pyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=C(Cl)C(OC=2N=C(OCCO)C=C(NS(=O)(=O)C=3C=CC(=CC=3)C(C)(C)C)N=2)=C1 YPNXXEIRGABVJB-UHFFFAOYSA-N 0.000 description 1
- XWEWXELBVQVFOR-UHFFFAOYSA-N 4-tert-butyl-n-[2-cyclopropyl-6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)pyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C2CC2)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 XWEWXELBVQVFOR-UHFFFAOYSA-N 0.000 description 1
- HRPPCBKROYTAKG-UHFFFAOYSA-N 4-tert-butyl-n-[5-(2-chloro-5-methoxyphenoxy)-6-(2-hydroxyethoxy)-2-(methoxymethyl)pyrimidin-4-yl]benzenesulfonamide Chemical compound C=1C(OC)=CC=C(Cl)C=1OC=1C(OCCO)=NC(COC)=NC=1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 HRPPCBKROYTAKG-UHFFFAOYSA-N 0.000 description 1
- RARBWVKPLLIETD-UHFFFAOYSA-N 4-tert-butyl-n-[5-[(2-chloro-5-methoxyphenyl)methyl]-6-(2-hydroxyethoxy)-2-morpholin-4-ylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=C(Cl)C(CC=2C(=NC(=NC=2NS(=O)(=O)C=2C=CC(=CC=2)C(C)(C)C)N2CCOCC2)OCCO)=C1 RARBWVKPLLIETD-UHFFFAOYSA-N 0.000 description 1
- QOPGXVVGPBNZHE-UHFFFAOYSA-N 4-tert-butyl-n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-propan-2-ylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C(C)C)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 QOPGXVVGPBNZHE-UHFFFAOYSA-N 0.000 description 1
- YNHOYNSAUVARLX-UHFFFAOYSA-N 4-tert-butyl-n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-propylpyrimidin-4-yl]benzenesulfonamide Chemical compound C=1C=CC=C(OC)C=1OC=1C(OCCO)=NC(CCC)=NC=1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 YNHOYNSAUVARLX-UHFFFAOYSA-N 0.000 description 1
- OBCTVWAIRIMFIJ-UHFFFAOYSA-N 4-tert-butyl-n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenyl)sulfanylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1SC(C(=NC=N1)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 OBCTVWAIRIMFIJ-UHFFFAOYSA-N 0.000 description 1
- QZQQQCPYBASFEN-UHFFFAOYSA-N 4-tert-butyl-n-[6-chloro-5-(2-methoxyphenoxy)-2-methylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC1=C(Cl)N=C(C)N=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 QZQQQCPYBASFEN-UHFFFAOYSA-N 0.000 description 1
- OIVLITBTBDPEFK-UHFFFAOYSA-N 5,6-dihydrouracil Chemical compound O=C1CCNC(=O)N1 OIVLITBTBDPEFK-UHFFFAOYSA-N 0.000 description 1
- PVXBVTOQDCSUNI-UHFFFAOYSA-N 5-(2-bromo-5-methoxyphenoxy)-4,6-dichloropyrimidine Chemical compound COC1=CC=C(Br)C(OC=2C(=NC=NC=2Cl)Cl)=C1 PVXBVTOQDCSUNI-UHFFFAOYSA-N 0.000 description 1
- LPHGHUZNQNNYEH-UHFFFAOYSA-N 5-(3,4-dimethoxyphenoxy)-4-hydroxy-1h-pyrimidin-6-one Chemical compound C1=C(OC)C(OC)=CC=C1OC1=C(O)N=CN=C1O LPHGHUZNQNNYEH-UHFFFAOYSA-N 0.000 description 1
- QULMQDVJMHVIOI-UHFFFAOYSA-N 5-[(2-chloro-5-methoxyphenyl)methyl]-2-morpholin-4-yl-1h-pyrimidine-4,6-dione Chemical compound COC1=CC=C(Cl)C(CC2C(N=C(NC2=O)N2CCOCC2)=O)=C1 QULMQDVJMHVIOI-UHFFFAOYSA-N 0.000 description 1
- IRPVABHDSJVBNZ-RTHVDDQRSA-N 5-[1-(cyclopropylmethyl)-5-[(1R,5S)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrazol-3-yl]-3-(trifluoromethyl)pyridin-2-amine Chemical compound C1=C(C(F)(F)F)C(N)=NC=C1C1=NN(CC2CC2)C(C2[C@@H]3CN(C[C@@H]32)C2COC2)=C1 IRPVABHDSJVBNZ-RTHVDDQRSA-N 0.000 description 1
- CCMKFQIHUKISAA-UHFFFAOYSA-N 6-[2-[tert-butyl(dimethyl)silyl]oxyethoxy]-5-(2-methoxyphenoxy)-2-pyrimidin-2-ylpyrimidin-4-amine Chemical compound COC1=CC=CC=C1OC1=C(N)N=C(C=2N=CC=CN=2)N=C1OCCO[Si](C)(C)C(C)(C)C CCMKFQIHUKISAA-UHFFFAOYSA-N 0.000 description 1
- XSTYKVVPROQPBV-UHFFFAOYSA-N 6-[2-[tert-butyl(dimethyl)silyl]oxyethoxy]-5-(2-methoxyphenoxy)pyrimidin-4-amine Chemical compound COC1=CC=CC=C1OC1=C(N)N=CN=C1OCCO[Si](C)(C)C(C)(C)C XSTYKVVPROQPBV-UHFFFAOYSA-N 0.000 description 1
- UYBNLIRUKAYVDR-UHFFFAOYSA-N 6-[2-[tert-butyl(dimethyl)silyl]oxyethoxy]-5-(3-methoxyphenoxy)pyrimidin-4-amine Chemical compound COC1=CC=CC(OC=2C(=NC=NC=2N)OCCO[Si](C)(C)C(C)(C)C)=C1 UYBNLIRUKAYVDR-UHFFFAOYSA-N 0.000 description 1
- TZGJDSUMWQJKTE-UHFFFAOYSA-N 6-chloro-5-(2-chloro-5-methoxyphenoxy)pyrimidin-4-amine Chemical compound COC1=CC=C(Cl)C(OC=2C(=NC=NC=2N)Cl)=C1 TZGJDSUMWQJKTE-UHFFFAOYSA-N 0.000 description 1
- CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- VXQQCLWDKVTFLF-UHFFFAOYSA-N C1(=CC=CC=C1)NC(=O)CNC(O)=O.N1CCCC1 Chemical compound C1(=CC=CC=C1)NC(=O)CNC(O)=O.N1CCCC1 VXQQCLWDKVTFLF-UHFFFAOYSA-N 0.000 description 1
- JRTFFECRELTPGK-UHFFFAOYSA-N CC(COC1=CC=CC=C1)(C(=O)O)C(=O)O Chemical compound CC(COC1=CC=CC=C1)(C(=O)O)C(=O)O JRTFFECRELTPGK-UHFFFAOYSA-N 0.000 description 1
- GLELEGCCWZPDQK-UHFFFAOYSA-N CC1=NOC(=C1)NC(O)=O.CC1=NOC(=C1)C(=O)N=[N+]=[N-] Chemical compound CC1=NOC(=C1)NC(O)=O.CC1=NOC(=C1)C(=O)N=[N+]=[N-] GLELEGCCWZPDQK-UHFFFAOYSA-N 0.000 description 1
- SSHZZSNTUOGBFN-UHFFFAOYSA-N COC1=CC=CC=C1OC(C(=NC(=N1)S(C)(=O)=O)S(=O)(=O)C=2C=CC(=CC=2)C(C)(C)C)=C1OCCOC(=O)C1=NC=CN1 Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)S(C)(=O)=O)S(=O)(=O)C=2C=CC(=CC=2)C(C)(C)C)=C1OCCOC(=O)C1=NC=CN1 SSHZZSNTUOGBFN-UHFFFAOYSA-N 0.000 description 1
- VLFWOIHJEKOINC-UHFFFAOYSA-N COC1=CC=CC=C1OC1(C=2N=CC=CN=2)N=C(NS(=O)(=O)C=2C=CC(CC(C)C)=CC=2)C=C(OCCO)N1 Chemical compound COC1=CC=CC=C1OC1(C=2N=CC=CN=2)N=C(NS(=O)(=O)C=2C=CC(CC(C)C)=CC=2)C=C(OCCO)N1 VLFWOIHJEKOINC-UHFFFAOYSA-N 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- PVADNUVQNKONPP-UHFFFAOYSA-N ClC1=C(C(=NC=N1)C1=C(C=CC=C1)S(=O)(=O)N)SC1=C(C=CC=C1)OC Chemical compound ClC1=C(C(=NC=N1)C1=C(C=CC=C1)S(=O)(=O)N)SC1=C(C=CC=C1)OC PVADNUVQNKONPP-UHFFFAOYSA-N 0.000 description 1
- RVQYLSGBWBPIDI-UHFFFAOYSA-N ClC1=C(OC2CN=C(NC2)SC)C=C(C=C1)OC Chemical compound ClC1=C(OC2CN=C(NC2)SC)C=C(C=C1)OC RVQYLSGBWBPIDI-UHFFFAOYSA-N 0.000 description 1
- GEVUSWWVZBMZRH-UHFFFAOYSA-N ClC1=C(OC=2C(=NC=NC2NS(=O)(=O)C2=CC3=C(OCCO3)C=C2)OC2=NC=CC=C2NC(O)=O)C=C(C=C1)OC Chemical compound ClC1=C(OC=2C(=NC=NC2NS(=O)(=O)C2=CC3=C(OCCO3)C=C2)OC2=NC=CC=C2NC(O)=O)C=C(C=C1)OC GEVUSWWVZBMZRH-UHFFFAOYSA-N 0.000 description 1
- CKBFSFXDRGSKIL-UHFFFAOYSA-N ClC1=NC=C(C(=N1)Cl)SC1=C(C=CC=C1)OC Chemical compound ClC1=NC=C(C(=N1)Cl)SC1=C(C=CC=C1)OC CKBFSFXDRGSKIL-UHFFFAOYSA-N 0.000 description 1
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
- 229930105110 Cyclosporin A Natural products 0.000 description 1
- 108010036949 Cyclosporine Proteins 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 239000004097 EU approved flavor enhancer Substances 0.000 description 1
- 102000030168 Endothelin A Receptor Human genes 0.000 description 1
- 108010090549 Endothelin A Receptor Proteins 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 208000010412 Glaucoma Diseases 0.000 description 1
- 206010018364 Glomerulonephritis Diseases 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 101001062535 Homo sapiens Follistatin-related protein 1 Proteins 0.000 description 1
- 101001122162 Homo sapiens Overexpressed in colon carcinoma 1 protein Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- 239000004909 Moisturizer Substances 0.000 description 1
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 1
- IHTHKEJMMYYLJW-UHFFFAOYSA-N N1(CCOCC1)C(CCC1=C(C=CC=C1)S(=O)(=O)N)=O.N1=C(C=CC=C1)NC(O)=O Chemical compound N1(CCOCC1)C(CCC1=C(C=CC=C1)S(=O)(=O)N)=O.N1=C(C=CC=C1)NC(O)=O IHTHKEJMMYYLJW-UHFFFAOYSA-N 0.000 description 1
- XSLVDRKENAPZIM-UHFFFAOYSA-N N1(CCOCC1)C1(C(C=CC=C1)NC(O)=O)F Chemical compound N1(CCOCC1)C1(C(C=CC=C1)NC(O)=O)F XSLVDRKENAPZIM-UHFFFAOYSA-N 0.000 description 1
- CXNYSKRKBPHREV-UHFFFAOYSA-N N1=C(C=CC=C1)C(=O)N=[N+]=[N-].N1=CC=CC=C1 Chemical compound N1=C(C=CC=C1)C(=O)N=[N+]=[N-].N1=CC=CC=C1 CXNYSKRKBPHREV-UHFFFAOYSA-N 0.000 description 1
- MVRQIFQKDMJRKU-UHFFFAOYSA-N N1=C(C=CC=C1)NC(O)=O.N1=C(C=CC=C1)C(=O)O.[N-]=[N+]=[N-] Chemical compound N1=C(C=CC=C1)NC(O)=O.N1=C(C=CC=C1)C(=O)O.[N-]=[N+]=[N-] MVRQIFQKDMJRKU-UHFFFAOYSA-N 0.000 description 1
- XJIVHXMICDEMNY-UHFFFAOYSA-N N1=C(C=CC=C1)NC(O)=O.N1=C(C=CC=C1)NC(O)=O Chemical compound N1=C(C=CC=C1)NC(O)=O.N1=C(C=CC=C1)NC(O)=O XJIVHXMICDEMNY-UHFFFAOYSA-N 0.000 description 1
- SIEMSBVFTHUMFC-UHFFFAOYSA-N N1=C(C=NC=C1)NC(O)=O.OCCOC1=C(C(=NC=N1)NS(=O)(=O)C1=CC(=C(C=C1)OC)OCC(=O)N1CCOCC1)OC1=C(C=CC=C1)OC Chemical compound N1=C(C=NC=C1)NC(O)=O.OCCOC1=C(C(=NC=N1)NS(=O)(=O)C1=CC(=C(C=C1)OC)OCC(=O)N1CCOCC1)OC1=C(C=CC=C1)OC SIEMSBVFTHUMFC-UHFFFAOYSA-N 0.000 description 1
- OFPCEWQBEHBQEG-UHFFFAOYSA-N N1=C(N=CC=C1)NC(O)=O.N1=C(C=NC=C1)C(=O)N=[N+]=[N-] Chemical compound N1=C(N=CC=C1)NC(O)=O.N1=C(C=NC=C1)C(=O)N=[N+]=[N-] OFPCEWQBEHBQEG-UHFFFAOYSA-N 0.000 description 1
- XIMAVBJUHUHCDZ-UHFFFAOYSA-N N1=CC=C(C=C1)NC(O)=O.N1=C(C=CC=C1)C(=O)N=[N+]=[N-] Chemical compound N1=CC=C(C=C1)NC(O)=O.N1=C(C=CC=C1)C(=O)N=[N+]=[N-] XIMAVBJUHUHCDZ-UHFFFAOYSA-N 0.000 description 1
- MGPAMVDJPPSZGW-UHFFFAOYSA-N N1=CC=C(C=C1)NC(O)=O.N1=CC=C(C=C1)C(=O)N=[N+]=[N-] Chemical compound N1=CC=C(C=C1)NC(O)=O.N1=CC=C(C=C1)C(=O)N=[N+]=[N-] MGPAMVDJPPSZGW-UHFFFAOYSA-N 0.000 description 1
- CHBWQDVGQWGGMS-UHFFFAOYSA-N N1C=NC(CC1=O)=O.Cl Chemical compound N1C=NC(CC1=O)=O.Cl CHBWQDVGQWGGMS-UHFFFAOYSA-N 0.000 description 1
- UHLVPJSBODRNTK-UHFFFAOYSA-N NCCOC1=C(C(=NC=N1)N(S(=O)(=O)C1=CC=CC=C1)C(C)(C)C)OC1=C(C=CC(=C1)OC)Cl Chemical compound NCCOC1=C(C(=NC=N1)N(S(=O)(=O)C1=CC=CC=C1)C(C)(C)C)OC1=C(C=CC(=C1)OC)Cl UHLVPJSBODRNTK-UHFFFAOYSA-N 0.000 description 1
- ZEUVZMNAKSYPJW-UHFFFAOYSA-N O1COC2=C1C=CC(=C2)COC(=O)C2=NC(=C(C=N2)OC2=C(C=CC(=C2)OC)Cl)NS(=O)(=O)C2=CC1=C(OCO1)C=C2 Chemical compound O1COC2=C1C=CC(=C2)COC(=O)C2=NC(=C(C=N2)OC2=C(C=CC(=C2)OC)Cl)NS(=O)(=O)C2=CC1=C(OCO1)C=C2 ZEUVZMNAKSYPJW-UHFFFAOYSA-N 0.000 description 1
- 102100027063 Overexpressed in colon carcinoma 1 protein Human genes 0.000 description 1
- 208000003782 Raynaud disease Diseases 0.000 description 1
- 208000012322 Raynaud phenomenon Diseases 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 206010038419 Renal colic Diseases 0.000 description 1
- 206010063897 Renal ischaemia Diseases 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- 208000032851 Subarachnoid Hemorrhage Diseases 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 206010047139 Vasoconstriction Diseases 0.000 description 1
- LXRZVMYMQHNYJB-UNXOBOICSA-N [(1R,2S,4R)-4-[[5-[4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate Chemical compound CC1=C(C=C(S1)C(=O)C1=C(N[C@H]2C[C@H](O)[C@@H](COS(N)(=O)=O)C2)N=CN=C1)[C@@H]1NCCC2=C1C=C(Cl)C=C2 LXRZVMYMQHNYJB-UNXOBOICSA-N 0.000 description 1
- JJSCUXAFAJEQGB-MRVPVSSYSA-N [(1r)-1-isocyanatoethyl]benzene Chemical compound O=C=N[C@H](C)C1=CC=CC=C1 JJSCUXAFAJEQGB-MRVPVSSYSA-N 0.000 description 1
- GRFUMPFWJKGLQC-SSDOTTSWSA-N [(1r)-1-phenylethyl]carbamic acid Chemical compound OC(=O)N[C@H](C)C1=CC=CC=C1 GRFUMPFWJKGLQC-SSDOTTSWSA-N 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 125000006383 alkylpyridyl group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 238000007098 aminolysis reaction Methods 0.000 description 1
- 210000000709 aorta Anatomy 0.000 description 1
- 210000002376 aorta thoracic Anatomy 0.000 description 1
- 150000005840 aryl radicals Chemical class 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- BNBQRQQYDMDJAH-UHFFFAOYSA-N benzodioxan Chemical compound C1=CC=C2OCCOC2=C1 BNBQRQQYDMDJAH-UHFFFAOYSA-N 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- 235000013877 carbamide Nutrition 0.000 description 1
- 150000001731 carboxylic acid azides Chemical class 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- QSKWJTXWJJOJFP-UHFFFAOYSA-N chloroform;ethoxyethane Chemical compound ClC(Cl)Cl.CCOCC QSKWJTXWJJOJFP-UHFFFAOYSA-N 0.000 description 1
- QQVDYSUDFZZPSU-UHFFFAOYSA-M chloromethylidene(dimethyl)azanium;chloride Chemical compound [Cl-].C[N+](C)=CCl QQVDYSUDFZZPSU-UHFFFAOYSA-M 0.000 description 1
- 229960001265 ciclosporin Drugs 0.000 description 1
- 229940061631 citric acid acetate Drugs 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- KQWGXHWJMSMDJJ-UHFFFAOYSA-N cyclohexyl isocyanate Chemical compound O=C=NC1CCCCC1 KQWGXHWJMSMDJJ-UHFFFAOYSA-N 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 229930182912 cyclosporin Natural products 0.000 description 1
- STORWMDPIHOSMF-UHFFFAOYSA-N decanoic acid;octanoic acid;propane-1,2,3-triol Chemical compound OCC(O)CO.CCCCCCCC(O)=O.CCCCCCCCCC(O)=O STORWMDPIHOSMF-UHFFFAOYSA-N 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
- 235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
- WBKFWQBXFREOFH-UHFFFAOYSA-N dichloromethane;ethyl acetate Chemical compound ClCCl.CCOC(C)=O WBKFWQBXFREOFH-UHFFFAOYSA-N 0.000 description 1
- AIHMBXSKURQVAQ-UHFFFAOYSA-N diethyl 2-[(2-chloro-5-methoxyphenyl)methyl]propanedioate Chemical compound CCOC(=O)C(C(=O)OCC)CC1=CC(OC)=CC=C1Cl AIHMBXSKURQVAQ-UHFFFAOYSA-N 0.000 description 1
- 230000010339 dilation Effects 0.000 description 1
- SBUXKADXTZOBJV-UHFFFAOYSA-N dimethyl 2-(2-methoxyphenoxy)propanedioate Chemical compound COC(=O)C(C(=O)OC)OC1=CC=CC=C1OC SBUXKADXTZOBJV-UHFFFAOYSA-N 0.000 description 1
- GSZYVUVXJMEXIB-UHFFFAOYSA-N dimethyl 2-(2-methoxyphenyl)sulfonylpropanedioate Chemical compound COC(=O)C(C(=O)OC)S(=O)(=O)C1=CC=CC=C1OC GSZYVUVXJMEXIB-UHFFFAOYSA-N 0.000 description 1
- LNBQBURECUEBKZ-UHFFFAOYSA-N dimethyl 2-chloropropanedioate Chemical compound COC(=O)C(Cl)C(=O)OC LNBQBURECUEBKZ-UHFFFAOYSA-N 0.000 description 1
- HCUYBXPSSCRKRF-UHFFFAOYSA-N diphosgene Chemical compound ClC(=O)OC(Cl)(Cl)Cl HCUYBXPSSCRKRF-UHFFFAOYSA-N 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 208000000718 duodenal ulcer Diseases 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- ZUBDGKVDJUIMQQ-ZTNLKOGPSA-N endothelin i Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@@H]2CSSC[C@@H](C(N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-ZTNLKOGPSA-N 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- WCQOBLXWLRDEQA-UHFFFAOYSA-N ethanimidamide;hydrochloride Chemical compound Cl.CC(N)=N WCQOBLXWLRDEQA-UHFFFAOYSA-N 0.000 description 1
- BEGBSFPALGFMJI-UHFFFAOYSA-N ethene;sodium Chemical group [Na].C=C BEGBSFPALGFMJI-UHFFFAOYSA-N 0.000 description 1
- SQEUYZKKYKRFTR-UHFFFAOYSA-N ethyl 2-[5-[[5-(2-chloro-5-methoxyphenoxy)-6-(2-hydroxyethoxy)pyrimidin-4-yl]sulfamoyl]-2-methoxyphenoxy]acetate Chemical compound C1=C(OC)C(OCC(=O)OCC)=CC(S(=O)(=O)NC=2C(=C(OCCO)N=CN=2)OC=2C(=CC=C(OC)C=2)Cl)=C1 SQEUYZKKYKRFTR-UHFFFAOYSA-N 0.000 description 1
- DUVOZUPPHBRJJO-UHFFFAOYSA-N ethyl 2-isocyanatoacetate Chemical compound CCOC(=O)CN=C=O DUVOZUPPHBRJJO-UHFFFAOYSA-N 0.000 description 1
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- WUDNUHPRLBTKOJ-UHFFFAOYSA-N ethyl isocyanate Chemical compound CCN=C=O WUDNUHPRLBTKOJ-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 235000019264 food flavour enhancer Nutrition 0.000 description 1
- YKSPDHDZLUZVDJ-UHFFFAOYSA-N furan-2-carbonyl azide Chemical compound [N-]=[N+]=NC(=O)C1=CC=CO1 YKSPDHDZLUZVDJ-UHFFFAOYSA-N 0.000 description 1
- XPFVYQJUAUNWIW-UHFFFAOYSA-N furfuryl alcohol Chemical compound OCC1=CC=CO1 XPFVYQJUAUNWIW-UHFFFAOYSA-N 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 201000005917 gastric ulcer Diseases 0.000 description 1
- 239000003365 glass fiber Substances 0.000 description 1
- 230000034659 glycolysis Effects 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- YDNLNVZZTACNJX-UHFFFAOYSA-N isocyanatomethylbenzene Chemical compound O=C=NCC1=CC=CC=C1 YDNLNVZZTACNJX-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- RHVNHKWMQOUSLJ-UHFFFAOYSA-N methoxymethanamine;hydrochloride Chemical compound Cl.COCN RHVNHKWMQOUSLJ-UHFFFAOYSA-N 0.000 description 1
- OJURWUUOVGOHJZ-UHFFFAOYSA-N methyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-(2-methoxy-2-oxoethyl)amino]ethyl]amino]acetate Chemical compound C=1C=CC=C(OC(C)=O)C=1CN(CC(=O)OC)CCN(CC(=O)OC)CC1=CC=CC=C1OC(C)=O OJURWUUOVGOHJZ-UHFFFAOYSA-N 0.000 description 1
- ATFKBWNEVZUSKC-UHFFFAOYSA-N methyl 2-isocyanatobenzoate Chemical compound COC(=O)C1=CC=CC=C1N=C=O ATFKBWNEVZUSKC-UHFFFAOYSA-N 0.000 description 1
- ZGEGCLOFRBLKSE-UHFFFAOYSA-N methylene hexane Natural products CCCCCC=C ZGEGCLOFRBLKSE-UHFFFAOYSA-N 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- XMWFMEYDRNJSOO-UHFFFAOYSA-N morpholine-4-carbonyl chloride Chemical compound ClC(=O)N1CCOCC1 XMWFMEYDRNJSOO-UHFFFAOYSA-N 0.000 description 1
- WCUWHUUPGXCMMQ-UHFFFAOYSA-N morpholine-4-carboximidamide Chemical compound NC(=N)N1CCOCC1 WCUWHUUPGXCMMQ-UHFFFAOYSA-N 0.000 description 1
- 125000006518 morpholino carbonyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])N(C(*)=O)C1([H])[H] 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- IVTHBHJRJOJFJH-UHFFFAOYSA-N n-[5-(2-bromo-5-methoxyphenoxy)-6-chloropyrimidin-4-yl]-4-tert-butylbenzenesulfonamide Chemical compound COC1=CC=C(Br)C(OC=2C(=NC=NC=2Cl)NS(=O)(=O)C=2C=CC(=CC=2)C(C)(C)C)=C1 IVTHBHJRJOJFJH-UHFFFAOYSA-N 0.000 description 1
- FRTNPCDZICVDEP-UHFFFAOYSA-N n-[5-(2-chloro-5-methoxyphenoxy)-6-(2-hydroxyethoxy)-2-(2-methoxyethyl)pyrimidin-4-yl]-1,3-benzodioxole-5-sulfonamide Chemical compound OCCOC1=NC(CCOC)=NC(NS(=O)(=O)C=2C=C3OCOC3=CC=2)=C1OC1=CC(OC)=CC=C1Cl FRTNPCDZICVDEP-UHFFFAOYSA-N 0.000 description 1
- KUIVQDODVIOICC-UHFFFAOYSA-N n-[5-(2-chloro-5-methoxyphenoxy)-6-(2-hydroxyethoxy)-2-(methoxymethyl)pyrimidin-4-yl]-1,3-benzodioxole-5-sulfonamide Chemical compound OCCOC1=NC(COC)=NC(NS(=O)(=O)C=2C=C3OCOC3=CC=2)=C1OC1=CC(OC)=CC=C1Cl KUIVQDODVIOICC-UHFFFAOYSA-N 0.000 description 1
- XAGCSCRHDFIFPX-UHFFFAOYSA-N n-[5-(2-chloro-5-methoxyphenoxy)-6-(2-hydroxyethoxy)pyrimidin-4-yl]-2,3-dihydro-1,4-benzodioxine-6-sulfonamide Chemical compound COC1=CC=C(Cl)C(OC=2C(=NC=NC=2NS(=O)(=O)C=2C=C3OCCOC3=CC=2)OCCO)=C1 XAGCSCRHDFIFPX-UHFFFAOYSA-N 0.000 description 1
- VUVQQLSVQFRREY-UHFFFAOYSA-N n-[5-(2-chloro-5-methoxyphenoxy)-6-(2-hydroxyethoxy)pyrimidin-4-yl]-4-(2-morpholin-4-yl-2-oxoethoxy)benzenesulfonamide Chemical compound COC1=CC=C(Cl)C(OC=2C(=NC=NC=2NS(=O)(=O)C=2C=CC(OCC(=O)N3CCOCC3)=CC=2)OCCO)=C1 VUVQQLSVQFRREY-UHFFFAOYSA-N 0.000 description 1
- NQVFZAMPHINZHM-UHFFFAOYSA-N n-[5-(2-chloro-5-methoxyphenoxy)-6-(2-hydroxyethoxy)pyrimidin-4-yl]-4-methoxy-3-(3-morpholin-4-yl-3-oxopropyl)benzenesulfonamide Chemical compound COC1=CC=C(Cl)C(OC=2C(=NC=NC=2NS(=O)(=O)C=2C=C(CCC(=O)N3CCOCC3)C(OC)=CC=2)OCCO)=C1 NQVFZAMPHINZHM-UHFFFAOYSA-N 0.000 description 1
- UERZWECTTNOGIS-UHFFFAOYSA-N n-[5-(2-chloro-5-methoxyphenoxy)-6-(2-hydroxyethoxy)pyrimidin-4-yl]-4-methoxy-3-propan-2-ylbenzenesulfonamide Chemical compound COC1=CC=C(Cl)C(OC=2C(=NC=NC=2NS(=O)(=O)C=2C=C(C(OC)=CC=2)C(C)C)OCCO)=C1 UERZWECTTNOGIS-UHFFFAOYSA-N 0.000 description 1
- BTXXUNWTTFDHHN-UHFFFAOYSA-N n-[6-(2-aminoethoxy)-5-(2-methoxyphenoxy)-2-methylpyrimidin-4-yl]-4-tert-butylbenzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(C)=N1)OCCN)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 BTXXUNWTTFDHHN-UHFFFAOYSA-N 0.000 description 1
- QZJICMANNNDNMW-UHFFFAOYSA-N n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-phenylpyrimidin-4-yl]-1,3-benzodioxole-5-sulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2C=CC=CC=2)OCCO)=C1NS(=O)(=O)C1=CC=C(OCO2)C2=C1 QZJICMANNNDNMW-UHFFFAOYSA-N 0.000 description 1
- IYJXBDKZDQMCSA-UHFFFAOYSA-N n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-pyrimidin-2-ylpyrimidin-4-yl]-4-methylsulfanylbenzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2N=CC=CN=2)OCCO)=C1NS(=O)(=O)C1=CC=C(SC)C=C1 IYJXBDKZDQMCSA-UHFFFAOYSA-N 0.000 description 1
- ZFFHBKBNZXRGEB-UHFFFAOYSA-N n-[6-chloro-5-(2-methoxyphenoxy)-2-phenylpyrimidin-4-yl]-1,3-benzodioxole-5-sulfonamide Chemical compound COC1=CC=CC=C1OC1=C(Cl)N=C(C=2C=CC=CC=2)N=C1NS(=O)(=O)C1=CC=C(OCO2)C2=C1 ZFFHBKBNZXRGEB-UHFFFAOYSA-N 0.000 description 1
- WNSXUAGCWVZDQC-UHFFFAOYSA-N n-ethylbenzenesulfonamide Chemical compound CCNS(=O)(=O)C1=CC=CC=C1 WNSXUAGCWVZDQC-UHFFFAOYSA-N 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- LCPDWSOZIOUXRV-UHFFFAOYSA-N phenoxyacetic acid Chemical compound OC(=O)COC1=CC=CC=C1 LCPDWSOZIOUXRV-UHFFFAOYSA-N 0.000 description 1
- KCTKOGAFDNEYIO-UHFFFAOYSA-N phenyl(trifluoromethyl)carbamic acid Chemical compound OC(=O)N(C(F)(F)F)C1=CC=CC=C1 KCTKOGAFDNEYIO-UHFFFAOYSA-N 0.000 description 1
- 229940081066 picolinic acid Drugs 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 208000002815 pulmonary hypertension Diseases 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- PTMBWNZJOQBTBK-UHFFFAOYSA-N pyridin-4-ylmethanol Chemical compound OCC1=CC=NC=C1 PTMBWNZJOQBTBK-UHFFFAOYSA-N 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- RBFMZSQIDDYMSX-UHFFFAOYSA-N pyrimidin-4-ylcarbamic acid Chemical compound OC(=O)NC1=CC=NC=N1 RBFMZSQIDDYMSX-UHFFFAOYSA-N 0.000 description 1
- SZSKAHAHBFDQKN-UHFFFAOYSA-N pyrimidine-2-carboximidamide Chemical compound NC(=N)C1=NC=CC=N1 SZSKAHAHBFDQKN-UHFFFAOYSA-N 0.000 description 1
- 239000002287 radioligand Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 238000005979 thermal decomposition reaction Methods 0.000 description 1
- VNMLVHLVBFHHSN-UHFFFAOYSA-N thiophen-2-ylcarbamic acid Chemical compound OC(=O)NC1=CC=CS1 VNMLVHLVBFHHSN-UHFFFAOYSA-N 0.000 description 1
- CTBMQGOJWHCMGI-UHFFFAOYSA-N thiophene-2-carbonyl azide Chemical compound [N-]=[N+]=NC(=O)C1=CC=CS1 CTBMQGOJWHCMGI-UHFFFAOYSA-N 0.000 description 1
- NBNQRDFVSOIHRV-UHFFFAOYSA-N thiophene-3-carbonyl azide Chemical compound [N-]=[N+]=NC(=O)C=1C=CSC=1 NBNQRDFVSOIHRV-UHFFFAOYSA-N 0.000 description 1
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 230000025033 vasoconstriction Effects 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/52—Two oxygen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/69—Benzenesulfonamido-pyrimidines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Ophthalmology & Optometry (AREA)
- Biomedical Technology (AREA)
- Pain & Pain Management (AREA)
- Vascular Medicine (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pulmonology (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Compositions Of Macromolecular Compounds (AREA)
- Pyridine Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH192493 | 1993-06-28 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SK77994A3 SK77994A3 (en) | 1995-03-08 |
| SK280736B6 true SK280736B6 (sk) | 2000-07-11 |
Family
ID=4221780
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK779-94A SK280736B6 (sk) | 1993-06-28 | 1994-06-28 | Sulfonylaminopyridíny, spôsob ich výroby, použitie |
Country Status (41)
| Country | Link |
|---|---|
| US (1) | US5541186A (da) |
| EP (1) | EP0633259B1 (da) |
| JP (1) | JP2545200B2 (da) |
| KR (1) | KR100338905B1 (da) |
| CN (1) | CN1050839C (da) |
| AT (1) | ATE175669T1 (da) |
| AU (1) | AU678467B2 (da) |
| BG (1) | BG61691B1 (da) |
| BR (2) | BR9402558A (da) |
| CA (1) | CA2125730C (da) |
| CO (1) | CO4230230A1 (da) |
| CZ (1) | CZ287184B6 (da) |
| DE (1) | DE59407626D1 (da) |
| DK (1) | DK0633259T3 (da) |
| EC (1) | ECSP941111A (da) |
| ES (1) | ES2127850T3 (da) |
| FI (1) | FI112944B (da) |
| GR (1) | GR3029874T3 (da) |
| HR (1) | HRP940370B1 (da) |
| HU (2) | HUT67636A (da) |
| IL (1) | IL110089A (da) |
| IS (1) | IS4185A (da) |
| LT (1) | LT3723B (da) |
| LV (1) | LV11175B (da) |
| MY (1) | MY110871A (da) |
| NO (1) | NO306403B1 (da) |
| NZ (1) | NZ260842A (da) |
| PE (1) | PE56794A1 (da) |
| PH (1) | PH30688A (da) |
| PL (2) | PL177031B1 (da) |
| RO (1) | RO114325B1 (da) |
| RU (1) | RU2142457C1 (da) |
| SG (1) | SG43888A1 (da) |
| SI (1) | SI0633259T1 (da) |
| SK (1) | SK280736B6 (da) |
| SV (1) | SV1994000028A (da) |
| TW (1) | TW394761B (da) |
| UA (1) | UA40578C2 (da) |
| UY (1) | UY23797A1 (da) |
| YU (1) | YU40794A (da) |
| ZA (1) | ZA944434B (da) |
Families Citing this family (69)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5514696A (en) * | 1992-05-06 | 1996-05-07 | Bristol-Myers Squibb Co. | Phenyl sulfonamide endothelin antagonists |
| US6743783B1 (en) * | 1993-12-01 | 2004-06-01 | Marine Polymer Technologies, Inc. | Pharmaceutical compositions comprising poly-β-1→4-N-acetylglucosamine |
| US6063911A (en) * | 1993-12-01 | 2000-05-16 | Marine Polymer Technologies, Inc. | Methods and compositions for treatment of cell proliferative disorders |
| US5612359A (en) * | 1994-08-26 | 1997-03-18 | Bristol-Myers Squibb Company | Substituted biphenyl isoxazole sulfonamides |
| EP0790826A4 (en) | 1994-11-16 | 1998-11-11 | Synaptic Pharma Corp | DIHYDROPYRIMIDINES AND THEIR USES |
| US6268369B1 (en) | 1994-11-16 | 2001-07-31 | Synaptic Pharmaceutical Corporation | 5-(heterocyclic alkyl)-6-aryl-dihydropyrimidines |
| CA2162630C (en) * | 1994-11-25 | 2007-05-01 | Volker Breu | Sulfonamides |
| RU2151767C1 (ru) * | 1994-12-20 | 2000-06-27 | Ф.Хоффманн-Ля Рош Аг | Сульфонамиды и фармацевтическая композиция |
| TW313568B (da) * | 1994-12-20 | 1997-08-21 | Hoffmann La Roche | |
| PT801062E (pt) * | 1994-12-28 | 2003-08-29 | Kowa Co | Derivados de pirimidina |
| US5760038A (en) * | 1995-02-06 | 1998-06-02 | Bristol-Myers Squibb Company | Substituted biphenyl sulfonamide endothelin antagonists |
| US5780473A (en) * | 1995-02-06 | 1998-07-14 | Bristol-Myers Squibb Company | Substituted biphenyl sulfonamide endothelin antagonists |
| US5573762A (en) * | 1995-04-24 | 1996-11-12 | Genentech, Inc. | Use of leukemia inhibitory factor specific antibodies and endothelin antagonists for treatment of cardiac hypertrophy |
| US5739333A (en) * | 1995-05-16 | 1998-04-14 | Tanabe Seiyaku Co., Ltd. | Sulfonamide derivative and process for preparing the same |
| US5846990A (en) * | 1995-07-24 | 1998-12-08 | Bristol-Myers Squibb Co. | Substituted biphenyl isoxazole sulfonamides |
| EP0852226B1 (en) * | 1995-09-06 | 2003-11-19 | Kowa Co. Ltd. | Pyrimidine derivatives |
| JPH09124620A (ja) | 1995-10-11 | 1997-05-13 | Bristol Myers Squibb Co | 置換ビフェニルスルホンアミドエンドセリン拮抗剤 |
| CZ260596A3 (en) * | 1995-10-12 | 1997-12-17 | Hoffmann La Roche | Sulfonamide derivative, process of its preparation and pharmaceutical composition containing thereof |
| US6228861B1 (en) | 1995-11-16 | 2001-05-08 | Synaptic Pharmaceutical Corporation | Dihydropyrimidines and uses thereof |
| WO1997022595A1 (en) * | 1995-12-20 | 1997-06-26 | Yamanouchi Pharmaceutical Co., Ltd. | Arylethenesulfonamide derivatives and drug composition containing the same |
| EP0904077A4 (en) | 1996-02-20 | 1999-12-22 | Bristol Myers Squibb Co | PROCESSES FOR THE PRODUCTION OF BIPHENYL ISOXAZOLE SULFAMIDES |
| US5856507A (en) * | 1997-01-21 | 1999-01-05 | Bristol-Myers Squibb Co. | Methods for the preparation of biphenyl isoxazole sulfonamides |
| US5939446A (en) * | 1996-04-09 | 1999-08-17 | Bristol-Myers Squibb Co. | Heteroaryl substituted phenyl isoxazole sulfonamide endothelin antagonists |
| US6172066B1 (en) | 1996-05-16 | 2001-01-09 | Synaptic Pharmaceutical Corporation | Dihydropyrimidines and uses thereof |
| US6245773B1 (en) | 1996-05-16 | 2001-06-12 | Synaptic Pharmaceutical Corporation | 5-(heterocyclic alkyl)-6-aryl-dihydropyrimidines |
| CA2265972A1 (en) * | 1996-09-16 | 1998-03-26 | Philip D. Acott | Use of igf-i for the treatment of polycystic kidney disease and related indications |
| TW536540B (en) * | 1997-01-30 | 2003-06-11 | Bristol Myers Squibb Co | Endothelin antagonists: N-[[2'-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl]-4-(2-oxazolyl)[1,1'-biphenyl]-2-yl]methyl]-N,3,3-trimethylbutanamide and N-(4,5-dimethyl-3-isoxazolyl)-2'-[(3,3-dimethyl-2-oxo-1-pyrrolidinyl)methyl]-4'-(2-oxazolyl)[1,1'-biphe |
| WO1998033781A1 (en) * | 1997-01-30 | 1998-08-06 | Bristol-Myers Squibb Company | Method for preventing or treating low renin hypertension by administering an endothelin antagonist |
| US6680323B2 (en) | 1998-12-23 | 2004-01-20 | Synaptic Pharmaceutical Corporation | Dihydropyrimidines and uses thereof |
| US6274585B1 (en) | 1998-12-23 | 2001-08-14 | Synaptic Pharmaceutical Corporation | Dihydropyrimidines and uses thereof |
| US7566452B1 (en) | 1999-05-04 | 2009-07-28 | New York University | Cancer treatment with endothelin receptor antagonists |
| CA2315614C (en) * | 1999-07-29 | 2004-11-02 | Pfizer Inc. | Pyrazoles |
| AU2001265871A1 (en) * | 2000-04-25 | 2001-11-07 | Actelion Pharmaceuticals Ltd | Substituted sulfonylaminopyrimidines |
| US6720324B2 (en) | 2000-07-05 | 2004-04-13 | Synaptic Pharmaceutical Corporation | Selective melanin concentrating hormone-1 (MCH1) receptor antagonists and uses thereof |
| MY140724A (en) | 2000-07-21 | 2010-01-15 | Actelion Pharmaceuticals Ltd | Novel arylethene-sulfonamides |
| US6670362B2 (en) | 2000-09-20 | 2003-12-30 | Pfizer Inc. | Pyridazine endothelin antagonists |
| JP2004509874A (ja) | 2000-09-25 | 2004-04-02 | アクテリオン ファマシューティカルズ リミテッド | 新規なアリールアルカン−スルフォンアミド類 |
| CN1935793B (zh) * | 2000-10-17 | 2010-06-23 | 庵原化学工业株式会社 | 取代的苯胺化合物的制备方法 |
| US6639082B2 (en) | 2000-10-17 | 2003-10-28 | Bristol-Myers Squibb Company | Methods for the preparation of biphenyl isoxazole sulfonamides |
| KR100374326B1 (ko) * | 2000-11-29 | 2003-03-03 | 한국과학기술연구원 | 6-히드록시-1, 3-디옥신-4-온 고리를 가진인간면역결핍바이러스 프로테아제 억제 화합물 및 그의제조방법 |
| HU229403B1 (en) | 2000-12-18 | 2013-12-30 | Actelion Pharmaceuticals Ltd | Novel sulfamides and their use as endothelin receptor antagonists |
| WO2002083650A1 (en) * | 2001-04-11 | 2002-10-24 | Actelion Pharmaceuticals Ltd | Novel sulfonylamino-pyrimidines |
| AU2011218661B2 (en) * | 2002-05-24 | 2012-07-05 | Millennium Pharmaceuticals, Inc. | CCR9 inhibitors and methods of use thereof |
| EP2399903A1 (en) * | 2002-05-24 | 2011-12-28 | Millennium Pharmaceuticals, Inc. | Ccr9 inhibitors and methods of use thereof |
| US7741519B2 (en) | 2007-04-23 | 2010-06-22 | Chemocentryx, Inc. | Bis-aryl sulfonamides |
| US7420055B2 (en) * | 2002-11-18 | 2008-09-02 | Chemocentryx, Inc. | Aryl sulfonamides |
| US7227035B2 (en) * | 2002-11-18 | 2007-06-05 | Chemocentryx | Bis-aryl sulfonamides |
| US6939885B2 (en) * | 2002-11-18 | 2005-09-06 | Chemocentryx | Aryl sulfonamides |
| JP4769460B2 (ja) * | 2002-12-02 | 2011-09-07 | アクテリオン ファーマシューティカルズ リミテッド | 新規スルファミド類 |
| DE102004027119A1 (de) | 2003-06-06 | 2004-12-30 | Schott Ag | UV-Strahlung absorbierendes Glas mit geringer Absorption im sichtbaren Bereich, ein Verfahren zu seiner Herstellung sowie dessen Verwendung |
| CN1930135B (zh) * | 2004-03-05 | 2011-12-28 | 弗·哈夫曼-拉罗切有限公司 | 作为p2x3和p2x2/3拮抗剂的二氨基嘧啶 |
| JP4926943B2 (ja) * | 2004-04-13 | 2012-05-09 | シンタ ファーマシューティカルズ コーポレーション | Il−12産生を阻害する二塩 |
| DK1763517T3 (da) * | 2004-06-28 | 2011-06-06 | Hoffmann La Roche | Pyrimidinderivater som 11beta-HSD1-inhibitorer |
| KR100847203B1 (ko) * | 2004-06-28 | 2008-07-17 | 에프. 호프만-라 로슈 아게 | 피리미딘 유도체 |
| TW200628467A (en) | 2004-11-11 | 2006-08-16 | Actelion Pharmaceuticals Ltd | Novel sulfamides |
| CA2620129C (en) | 2005-09-01 | 2014-12-23 | F. Hoffmann-La Roche Ag | Diaminopyrimidines as p2x3 and p2x2/3 modulators |
| WO2007025900A1 (en) * | 2005-09-01 | 2007-03-08 | F. Hoffmann-La Roche Ag | Diaminopyrimidines as p2x3 and p3x2/3 modulators |
| CA2619919C (en) * | 2005-09-01 | 2014-04-01 | F. Hoffmann-La Roche Ag | Diaminopyrimidines as p2x3 and p2x2/3 modulators |
| MX2008011842A (es) * | 2006-03-13 | 2008-10-02 | Encysive Pharmaceuticals Inc | Procedimientos y composiciones para el tratamiento de insuficiencia cardiaca diastolica. |
| MX2008011844A (es) * | 2006-03-13 | 2008-10-02 | Encysive Pharmaceuticals Inc | Formulaciones de sitaxsentano de sodio. |
| US20080026061A1 (en) * | 2006-06-22 | 2008-01-31 | Reichwein John F | Crystalline N-(4-chloro-3-methyl-5-isoxazolyl)-2-[2-methyl-4.5-(methylenedioxy)phenylacetyl]-thiophene-3-sulfonamide |
| AR062501A1 (es) | 2006-08-29 | 2008-11-12 | Actelion Pharmaceuticals Ltd | Composiciones terapeuticas |
| US8871247B2 (en) | 2007-02-19 | 2014-10-28 | Marine Polymer Technologies, Inc. | Hemostatic compositions and therapeutic regimens |
| MX2010001837A (es) | 2007-08-17 | 2010-03-10 | Actelion Pharmaceuticals Ltd | Derivados de 4-pirimidinasulfamida. |
| WO2011130646A1 (en) | 2010-04-15 | 2011-10-20 | Marine Polymer Technologies, Inc. | Anti-bacterial applications of poly -n-acetylglucosamine nanofibers |
| NZ732118A (en) | 2011-04-15 | 2018-11-30 | Marine Polymer Tech Inc | Treatment of disease with poly-n-acetylglucosamine nanofibers |
| RU2604060C1 (ru) * | 2015-10-06 | 2016-12-10 | федеральное государственное бюджетное образовательное учреждение высшего образования "Санкт-Петербургская государственная химико-фармацевтическая академия" Министерства здравоохранения Российской Федерации (ФГБОУ ВО СПХФА Минздрава России) | Способ получения 2,5-дизамещенных 6-гидроксипиримидин-4(3н)-онов |
| AR107928A1 (es) | 2016-03-22 | 2018-06-28 | Merck Sharp & Dohme | Moduladores alostéricos de receptores de acetilcolina nicotínicos |
| RU2643356C2 (ru) * | 2016-06-22 | 2018-02-01 | федеральное государственное бюджетное образовательное учреждение высшего образования "Волгоградский государственный медицинский университет" Министерства здравоохранения Российской Федерации | Новое n-арилсульфамидное производное о-бензоиламинобензойной кислоты, обладающее анксиолитической, актопротекторной и антидепрессивной активностью |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0210526B1 (de) | 1985-07-24 | 1989-05-24 | Siemens Aktiengesellschaft | Kernreaktorbrennelement |
| TW270116B (da) * | 1991-04-25 | 1996-02-11 | Hoffmann La Roche | |
| RU2086544C1 (ru) | 1991-06-13 | 1997-08-10 | Хоффманн-Ля Рош АГ | Бензолсульфонамидные производные пиримидина или их соли, фармацевтическая композиция для лечения заболеваний, связанных с активностью эндотелина |
| TW287160B (da) * | 1992-12-10 | 1996-10-01 | Hoffmann La Roche |
-
1994
- 1994-06-08 TW TW083105221A patent/TW394761B/zh not_active IP Right Cessation
- 1994-06-13 CA CA002125730A patent/CA2125730C/en not_active Expired - Fee Related
- 1994-06-16 ES ES94109257T patent/ES2127850T3/es not_active Expired - Lifetime
- 1994-06-16 SG SG1996004116A patent/SG43888A1/en unknown
- 1994-06-16 EP EP94109257A patent/EP0633259B1/de not_active Expired - Lifetime
- 1994-06-16 DK DK94109257T patent/DK0633259T3/da active
- 1994-06-16 AT AT94109257T patent/ATE175669T1/de active
- 1994-06-16 DE DE59407626T patent/DE59407626D1/de not_active Expired - Lifetime
- 1994-06-16 SI SI9430236T patent/SI0633259T1/xx unknown
- 1994-06-21 ZA ZA944434A patent/ZA944434B/xx unknown
- 1994-06-22 IL IL11008994A patent/IL110089A/xx not_active IP Right Cessation
- 1994-06-24 IS IS4185A patent/IS4185A/is unknown
- 1994-06-24 AU AU65948/94A patent/AU678467B2/en not_active Ceased
- 1994-06-24 NZ NZ260842A patent/NZ260842A/en unknown
- 1994-06-24 HR HR01924/93-6A patent/HRP940370B1/xx not_active IP Right Cessation
- 1994-06-24 HU HU9401907A patent/HUT67636A/hu unknown
- 1994-06-27 PL PL94323036A patent/PL177031B1/pl unknown
- 1994-06-27 PL PL94304007A patent/PL175771B1/pl unknown
- 1994-06-27 CO CO94027814A patent/CO4230230A1/es unknown
- 1994-06-27 LV LVP-94-131A patent/LV11175B/lv unknown
- 1994-06-27 LT LTIP1979A patent/LT3723B/lt not_active IP Right Cessation
- 1994-06-27 MY MYPI94001661A patent/MY110871A/en unknown
- 1994-06-27 NO NO942428A patent/NO306403B1/no unknown
- 1994-06-27 FI FI943084A patent/FI112944B/fi not_active IP Right Cessation
- 1994-06-27 EC EC1994001111A patent/ECSP941111A/es unknown
- 1994-06-27 US US08/266,072 patent/US5541186A/en not_active Expired - Lifetime
- 1994-06-27 PE PE1994245279A patent/PE56794A1/es not_active Application Discontinuation
- 1994-06-27 CZ CZ19941573A patent/CZ287184B6/cs not_active IP Right Cessation
- 1994-06-27 BR BR9402558A patent/BR9402558A/pt not_active Application Discontinuation
- 1994-06-27 RU RU94022258/04A patent/RU2142457C1/ru not_active IP Right Cessation
- 1994-06-27 BG BG98880A patent/BG61691B1/bg unknown
- 1994-06-27 PH PH48525A patent/PH30688A/en unknown
- 1994-06-27 YU YU40794A patent/YU40794A/sh unknown
- 1994-06-27 CN CN94106574A patent/CN1050839C/zh not_active Expired - Fee Related
- 1994-06-27 UA UA94005281A patent/UA40578C2/uk unknown
- 1994-06-27 UY UY23797A patent/UY23797A1/es not_active IP Right Cessation
- 1994-06-27 KR KR1019940014774A patent/KR100338905B1/ko not_active Expired - Fee Related
- 1994-06-28 SV SV1994B00028A patent/SV1994000028A/es not_active Application Discontinuation
- 1994-06-28 RO RO94-01112A patent/RO114325B1/ro unknown
- 1994-06-28 JP JP6146003A patent/JP2545200B2/ja not_active Expired - Fee Related
- 1994-06-28 SK SK779-94A patent/SK280736B6/sk unknown
-
1995
- 1995-06-21 HU HU95P/P00298P patent/HU211533A9/hu unknown
-
1996
- 1996-12-05 BR BR1100089-9A patent/BR1100089A/pt active IP Right Grant
-
1999
- 1999-04-05 GR GR990400963T patent/GR3029874T3/el unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| SK280736B6 (sk) | Sulfonylaminopyridíny, spôsob ich výroby, použitie | |
| CN1098254C (zh) | 新的磺酰胺 | |
| BG60831B2 (bg) | Нови сулфонамиди | |
| NO324952B1 (no) | Nye sulfonamider, fremstilling av disse, farmasoytiske preparater inneholdende slike,anvendelse av disse forbindelsene som medikament samt anvendelse av disse for fremstilling av medikament for behandling av lidelser. | |
| RU2162084C2 (ru) | Сульфонамиды и фармацевтический препарат | |
| US7091201B2 (en) | Arylalkane-sulfonamides having endothelin-antagonist activity | |
| PL185692B1 (pl) | Nowe sulfonamidy, sposób ich wytwarzania oraz zawierające je preparaty farmaceutyczne | |
| EP1322624B1 (en) | Arylalkane-sulfonamides having endothelin-antagonist activity | |
| JPH0899961A (ja) | ベンゼンスルホンアミド誘導体及びその製法 | |
| MXPA97004587A (es) | Sulfonamidas novedosas |